We previously performed gene expression profile analyses of 20 intestinal-type gastric cancers, and identified a set of genes whose expression levels were elevated in cancer tissues compared to their corresponding non-cancerous tissues. In the present study we focused on the immunoglobulin superfamily 11 gene (IGSF11). Its expression was also elevated in colorectal cancers and hepatocellular carcinomas as well as intestinal-type gastric cancers. Northern blot analysis showed that it was expressed abundantly in testis and ovary. These data suggest that IGSF11 is a good candidate of cancer-testis antigen. Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer cells. To investigate the possibility of clinical application of peptide vaccine to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested whether the peptides elicit IGSF11-specific CTL. As a result, we successfully established oligo-clonal CTL by stimulation with IGSF11-9-207 (ALSSGLYQC). In addition, we also established additional CTL using IGSF11-9V (ALSSGLYQV), anchor-modified peptides of IGSF11-9-207. These peptides showed IGSF11-specific cytotoxic activity in an HLA-A*0201-restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy. These findings have provided a novel insight into carcinogenesis of the stomach, colon and liver, and will be helpful for the development of novel therapeutic strategies to a wide range of human cancers.
Despite the discovery of multiple TAAs, only a limited number is available for clinical application, particularly against epithelial malignancies. In this study we searched for novel TAAs using expression profiles of gastric cancer examined with cDNA microarray, and identified the SCRN1 gene as a candidate. SCRN1 was confirmed to be expressed in five out of seven gastric cancers with semiquantitative RT-PCR. With Northern blot analysis, it was detected abundantly in the testis and ovary, but it was barely detectable in 14 other normal human adult organs. Colony formation assay revealed that its augmented expression is associated with promoted cell growth. As these expression profiles and functional features of SCRN1 appeared to be compatible with the characteristics of the hypothesized ideal TAAs, we examined whether SCRN1 protein contains antigenic epitope peptides restricted to HLA-A*0201. We synthesized the candidate peptides derived from SCRN1, and tried to induce CTLs with each peptide. The CTL clones were successfully induced with a peptide SCRN1-196 (KMDAEHPEL), and they lyzed not only the peptide-pulsed targets but also the tumor cells expressing both SCRN1 and HLA-A*0201 endogenously. These results strongly suggest that SCRN1-196 is an epitope peptide restricted to HLA-A*0201. Furthermore, we synthesized an anchor-modified peptide SCRN1-9 V (KMDAEHPEV), in which leucine at position 9 was substituted for valine to increase the binding affinity to the HLA-A*0201 molecules. The CTL clones induced by SCRN1-9 V also recognized tumor cells expressing its natural SCRN1 protein endogenously. These results strongly suggest that SCRN1 is a novel TAA and these peptides, both native and modified, may be applicable for cancer vaccines to treat gastric cancer. (Cancer Sci 2006; 97: 411-419)
Pheochromocytomas are rare neuroendocrine tumors that produce symptoms through the excess release of catecholamines. The treatment of choice is a complete surgical removal after pretreatment with an α-blocker, to prevent dangerous hemodynamic fluctuations. Newell and colleagues defined the rare, fatal condition of catecholamine crisis, which includes multiple organ failure (MOF), severe blood pressure variability, high fever, and encephalopathy, as pheochromocytoma multisystem crisis (PMC). The indications for emergency surgery in this unstable state still remain controversial. This report presents the case of a 52-year-old female patient with PMC who successfully underwent a surgical resection. This case showed that early tumor removal may be the only means of halting the progression of this disease.
Few reports have been concerned with the risk of needle track dissemination of tumor cells following fine-needle aspiration biopsy, especially for follicular thyroid nodules. A 61-year-old woman who underwent fine-needle aspiration biopsy and surgery 5 years previously for follicular thyroid adenoma presented with nodules that had developed in the sternocleidomastoid and omohyoid muscles of the anterior neck. These nodules were located along a line from the skin to the thyroid that coincided with the needle track of the previous biopsy. Following surgical resection, histological diagnosis determined the nodules to be follicular carcinoma. The clinical course and linear arrangement of the lesions were highly suggestive of needle track dissemination of tumor cells following fine-needle aspiration biopsy. Although fine-needle aspiration biopsy is a useful tool for the diagnosis of thyroid nodules, it is important to consider the risk of tumor cell dissemination.
Laparoscopic total adrenalectomy has become a standard technique for small adrenal tumors; however, bilateral adrenalectomy results in postoperative adrenal insufficiency, necessitating lifelong steroid replacement. To preserve adrenocortical function in a 41-year-old woman with bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome, we performed laparoscopic bilateral partial adrenalectomy. We based our preoperative diagnosis of bilateral adrenocortical tumors causing Cushing's syndrome on the results of endocrinological investigations and imaging findings. Thus, we performed lateral transperitoneal laparoscopic bilateral partial adrenalectomy, preserving the adrenal glands, which were normal. Pathological examination of both tumors confirmed the diagnosis of adrenocortical adenoma. The patient had no postoperative complications, and her adrenocortical function was normal without steroid replacement at her 10-month follow-up. This report shows that Cushing's syndrome resulting from bilateral adenomas can be effectively treated by laparoscopic bilateral partial adrenalectomy as a minimally invasive, adrenocortical-preserving operation.
A 41-year-old woman presented with severe and sudden anterior neck swelling, pain, and dysphagia. Computed tomography (CT) scan and ultrasound of the neck showed a giant mass in the retropharyngeal space, displacing the trachea and esophagus anteriorly. Aspiration cytology was done, following which extensive cervical and chest ecchymosis occurred and her symptoms immediately improved. A repeat CT scan demonstrated that the cervical giant mass had vanished, but there was a residual mass in the left paratracheal space. Exploratory surgery of the neck revealed a parathyroid cyst with severe adhesion to the surrounding tissues. We considered that a ruptured parathyroid cyst had induced massive hemorrhage into the cervical tissues and mediastinum, but that the hemorrhage had been absorbed. Extracapsular hemorrhage from a parathyroid adenoma or cyst is rare, especially from a parathyroid cyst. In fact, to our knowledge, this represents only the third case of symptomatic spontaneous bleeding of a parathyroid cyst. Nevertheless, this entity should still be considered in the differential diagnosis of all rapidly progressing retropharyngeal masses.
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