Immunohistochemical Expression of Blood Group Substances and Related Carbohydrate Antigens in Breast Carcinoma

In forty–one carcinomas and sixteen benign lesions (fibroadenoma and mastopathy) of the human breast, immunohistochemical expression of sialylated and non–sialylated forms of both Le^a and Le^x, and the A, B, and H type 2 blood group substances were studied by using an indirect immunoperoxidase staining. In normal ductal epithelium and benign lesion of breast, Lewis–related antigens were mostly expressed. Breast carcinomas showed these antigens with the following frequencies: Le^a, 31.7% (13/41); sialyl Le^a, 56.1% (23/41); Le^x, 46.3% (19/41); sialyl Le^x, 68.3% (28/41); A/B/H type 2, 38.1% (16/41). Sialylated forms of Le^a and Le^x were observed more frequently than their respective non–sialylated forms in breast carcinomas. In both one normal epithelium and four carcinomas of breast with Le^(a?b-) phenotype, the expressions of type 2 antigens were observed, while type 1 antigens were not consistently expressed. Although compatible expression was observed in all specimens of both normal epithelium and benign lesion of breast, twenty–four cases with the deletion of A and/or B antigens, six cases with H type 2 accumulation and one case with incompatible expression were demonstrated in breast carcinoma. Thirty–one breast carcinomas which showed the deletion of A/B/H type 2 expressed the Lewis–related antigens more frequently than nine cases which showed compatible expression. These results suggested that the activation of terminal fucosyltransferase and sialyltransferase as well as inactivation of some glycosyltransferases had occurred in cancer cell membrane, and sialyl Le¹, defined by a new monoclonal antibody CSLEX1, may be useful as a tumor–associated antigen independent of Lewis blood group type in breast cancer.     

Developmental outcomes in persistent pulmonary hypertension treated with nitric oxide therapy

Background:  The aim of the present study was to assess 3 year auditory and neurodevelopmental outcomes of persistent pulmonary hypertension of the newborn (PPHN) before and after introducing inhaled nitric oxide (i-NO) therapy, and to detect the clinical factors affecting poor outcome.
Methods:  A retrospective historical cohort study of 26 survivors with PPHN with oxygenation index (OI) ≥25 (13 infants without i-NO therapy, control group; 13 with i-NO therapy, i-NO group) was performed. Auditory brainstem response (ABR) at 6 and 12 months and neurodevelopmental outcomes at 3 years of age were evaluated.
Results:  ABR abnormalities at 6 months were observed in one infant in the i-NO group and six in the control group ( P  = 0.04). At 1 year, one infant in the i-NO group and two of six infants in the control group still had ABR abnormality. In the i-NO group, two children had abnormal neurodevelopmental outcomes, as compared with five children in the control group at 3 year follow up. Two children in the control group and no children in the i-NO group had hearing loss at 3 years of age. Hypocapnea ( P  = 0.04) and elevated creatine phosphokinase ( P  = 0.04) were found to be most predictive for neurodevelopmental abnormality.
Conclusion:  Avoidance of excessive hypocapnea via introduction of i-NO therapy might reduce both ABR and neurodevelopmental abnormalities.     

Case of Gastric Lymphoma Diagnosed by Laparoscopic Excision Biopsy

Primary gastric lymphoma is a relatively uncommon disease and sometimes forms submucosal growth causing difficulty of diagnosis. We have reported a case of primary gastric lymphoma successfully diagnosed by laparoscopic wedge resection, after repeatedly performing endoscopic forcep biopsies. Diagnostic laparoscopy for obtaining definite histological diagnosis can be regarded as minimally invasive, accurate and safe.     

Clinicopathological features of malignant intraductal papillary mucinous tumors of the pancreas: the differential diagnosis from benign entities

BACKGROUND: The accurate differential diagnosis of malignant intraductal papillary mucinous tumors (IPMTs) of the pancreas from benign IPMTs remains unclear. HYPOTHESIS: Predictive factors for differentiating malignant IPMTs from benign IPMTs can be documented. DESIGN: Retrospective study (1999-2003). SETTING: Wakayama Medical University Hospital, Wakayama, Japan. PATIENTS: Twenty-seven consecutive patients with IPMTs (11 with adenoma, 3 with dysplasia, 5 with adenocarcinoma, and 8 with invasive adenocarcinoma) who underwent surgery were retrospectively analyzed in terms of clinicopathological features. MAIN OUTCOME MEASURE: Clinical data, preoperative imaging findings, cytology, and tumor marker level, including carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), in serum and pure pancreatic juice. RESULTS: In preoperative imaging findings, the mean tumor size for the malignant IPMT group (81 +/- 18 mm) was significantly larger than that for the benign IPMT group (31 +/- 4 mm) (P =.002). The mean mural nodule size for the malignant IPMT group (9.8 +/- 4.4 mm) was significantly larger than that for the benign IPMT group (3.3 +/- 5.7 mm) (P =.002). The CEA levels in pure pancreatic juice in the malignant IPMT group (3051 +/- 7556 ng/mL) were significantly higher than in the benign IPMT group (41 +/- 80 ng/mL) (P =.003), although no significant differences in cytologic analyses and CA19-9 levels in pure pancreatic juice were found between the 2 groups. CONCLUSION: Our findings suggest that tumor size larger than 30 mm, mural nodule size larger than 5 mm, and CEA levels higher than 110 ng/mL in pure pancreatic juice were predictive factors for diagnosis of malignant IPMTs.     

Clinical outcomes of definitive radiotherapy for patients with cT1aN0M0 esophageal cancer unsuitable for endoscopic resection and surgery

BackgroundStudies on the clinical outcomes of radiotherapy for clinical (c)T1aN0M0 (UICC-TNM Classification, Eighth Edition) esophageal cancer (EC) are limited. Therefore, this retrospective study aimed to clarify the clinical outcomes of definitive radiotherapy (RT) or chemoradiotherapy (CRT) for cT1aN0M0 EC unsuitable for endoscopic resection and surgery.MethodsPatients with cT1aN0M0 esophageal squamous cell carcinoma who underwent definitive RT or CRT between January 2009 and December 2020 were retrospectively reviewed. The initial response, toxicities, survival rates, recurrence patterns, and salvage treatments of the patients were evaluated. Initial response was measured using the Response Evaluation Criteria in Solid Tumors guideline. Toxicity was assessed and documented following the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Survival rates from the date of initiation of treatment were measured using the Kaplan–Meier method.ResultsTwenty patients treated with definitive RT or CRT were included in the study. The median follow-up duration was 55 months (range, 13–131 months). All patients achieved complete response to the initial treatment. Grade 3 acute toxicities observed esophagitis (10%), pneumonitis (5%), and leukopenia (5%). Late toxicities higher than grade 3 were not observed. The 1-, 3-, and 5-year overall and disease-specific survival rates were 100% and 100%, 83% and 100%, and 67% and 100%, respectively. No treatment-related deaths occurred. Among the 20 patients, 6 showed local recurrence and 2 showed metachronous recurrence. Seven patients underwent salvage endoscopic submucosal dissection (ESD), and one underwent argon plasma coagulation treatment. After the endoscopic treatment, no recurrences were observed.ConclusionsDefinitive RT or CRT was considered an alternative initial treatment for patients with cT1aN0M0 EC who were unsuitable for endoscopic resection and surgery.     

Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cydooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer. (Cancer Sci 2003; 94: 355–359)     

Longitudinal association of vascular and Alzheimer's dementias, diabetes, and glucose tolerance

OBJECTIVE: To assess the relationship between impaired glucose tolerance and both vascular dementia and AD. BACKGROUND: Diabetes and abnormalities of glucose metabolism have been associated with stroke and poor cognitive function. In addition, glycoproteins and glycosylation have been postulated to be associated with the development of neuritic plaques characteristic of AD. METHODS: A historical prospective cohort study of Japanese-American men (n = 3,774), who were examined at ages 45 to 68 (1965 through 1968) and again at ages 71 to 93 (1991 through 1993). Measurements were obtained by clinical and home examinations: assessment of glucose intolerance (nonfasting 1 hour after glucose load) from 1965 through 1968 and history of diabetes diagnosed by a physician at examinations given from 1965 through 1968 and from 1976 through 1978. At the 1991 through 1993 examinations, the Cognitive Assessment Screening Instrument (CASI)-an instrument designed for use in cross-cultural settings combining features of the Folstein Mini-Mental State Examination, the Modified Mini-Mental State Examination, and the Hasegawa Dementia Screening Scale-was used. Diagnosis and classification of AD and vascular dementia were made by a consensus panel using neuropsychologic assessment data, a neurologist's evaluation, and information from a family informant. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria were used to establish dementia, and subclassification by cause was based on other published criteria. RESULTS: No association between AD and diabetes, present either 25 or 15 years previously, was found after adjustment for age and education in a multiple regression model. A significant association was found between impaired glucose tolerance at baseline and vascular dementia (p < 0.01). CONCLUSIONS: These findings confirm expected relationships between impaired glucose tolerance and stroke-related dementia but do not support an association of disordered glucose metabolism with AD.     

Identification of synaptic activity-dependent genes by exposure of cultured cortical neurons to tetrodotoxin followed by its withdrawal

Activity-dependent gene expression is one of the key mechanisms of synaptic plasticity that form the basis of higher order functions such as learning and memory. In the present study, we surveyed for activity-dependent genes by analyzing gene expression changes accompanying reversible inhibition of synaptic activity by tetrodotoxin (TTX) using two types of DNA microarrays; our focused oligo DNA microarray "Synaptoarray" and the commercially available high-density array. Cerebral cortical cells from E18 rat embryos were cultured for 14 days to ensure synaptogenesis, then treated with 1 muM TTX for 48 hr without detectable effect on cell viability. Synaptic density estimated by the amount of Synapsin I and Synaptotagmin I was decreased 21-24% by TTX treatment, but recovered to the control level 48 hr after TTX withdrawal. Comparison of gene expression profiles by competitive hybridization of fluorescently labeled cRNA from TTX-treated and control cells showed an overall downregulation of the genes on the Synaptoarray by TTX-treatment with different recovery rates after TTX withdrawal. With 16 representative genes, microarray data were validated by real-time PCR analysis. Genes most severely downregulated by TTX and upregulated above the control level at 5 hr after TTX withdrawal were munc13-1 (involved in docking and priming of synaptic vesicles) and Shank2 (involved in the postsynaptic scaffold). In addition, comprehensive screening at 5 hr after TTX withdrawal using high density arrays resulted in additional identification of Rgs2, a regulator of trimeric G-protein signaling, as an activity-dependent gene. These three genes are thus likely to be key factors in the regulation of synaptic plasticity. (c) 2007 Wiley-Liss, Inc.