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Biomedical subjects

K Haruma

Publications and source records attributed to K Haruma.

At least 73 records · Page 4Linked to original sources

Evaluation of lower oesophageal sphincter pressure using endoscopic manometric sleeve assembly.

BACKGROUND: The purpose of this study was to establish a method to determine lower oesophageal sphincter (LOS) pressure using an endoscopic manometric sleeve assembly. METHODS: We used a 250-cm, three-lumen, 2.2-mm external diameter silicon catheter with a 3-cm sleeve sensor that was passed easily through the biopsy channel (2.8 mm diameter) of the gastroscope. Each lumen was perfused with distilled water using a low-compliance, pneumohydraulic capillary infusion system. Forty-seven healthy subjects and 35 patients with oesophageal disorders underwent study during routine diagnostic endoscopy. In 27 of the subjects, standard transnasal manometry with a three-lumen, 4.5-mm diameter polyvinyl catheter with a 5-cm sleeve sensor was also performed. RESULTS: Lower oesophageal sphincter pressure (LOS) was evaluated in all subjects (median pressure 16 mmHg, range 0-55 mmHg) for 6 min during routine endoscopic examination. The LOS pressure readings between standard and endoscopic manometry correlated well. The LOS pressure was significantly lower in healthy subjects with hiatal hernia than in those without hernia and was also significantly lower in patients with reflux oesophagitis than in healthy subjects. CONCLUSIONS: Endoscopic manometric sleeve assembly was used during routine endoscopic examination and was useful for easily determining LOS pressure. It could be used for evaluation of oesophageal motility disorders, thus avoiding the use of a more invasive and time-consuming method.

Case-Control Studies↗

Effect of age and Helicobacter pylori infection on gastric acid secretion.

BACKGROUND: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection. METHODS: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0-4. RESULTS: Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age. CONCLUSIONS: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age.

Adolescent↗

Enhanced tumorigenicity of insulinoma by X-irradiation of the gastric regions in Sprague-Dawley male rats.

BACKGROUND AND AIMS: There has been no suitable animal model for human insulinoma because incidence of pancreatic tumours induced by whole-body irradiation or chemicals has been very low. The purpose of this study was to establish an experimental model with a high incidence of insulinoma. The induction of islet cell tumour by X-irradiation was investigated. METHODS: Forty Sprague-Dawley male rats were used in this study. Twenty-eight rats were irradiated with two 10-Gy doses to the gastric region at a 3-day interval, and 12 rats not subjected to X-irradiation served as a control group. The rats were killed 16 months after the first irradiation. Expression of insulin mRNA and protein was examined by northern blot analysis and immunohistochemistry, respectively. Rat serum insulin and glucose levels were measured using enzyme-linked immunosorbent assay. RESULTS: Tumour incidence was 89.3% (25/28) in X-ray group and 8.3% (1/12) in the control group (P < 0.05). Pancreatic tumours, which appeared in all 25 rats with tumours, showed the highest incidence of all neoplasms detected. Tumour cells showed strong immunoreactivity for insulin in 20 of 25 pancreatic tumours (80%). Expression of insulin mRNA was confirmed by northern blot analysis. Furthermore, rats with pancreatic tumours had lower serum glucose levels and higher insulin levels than the control rats. CONCLUSION: X-irradiated SD rats may be considered a suitable model for insulinoma because of their high tumorigenicity.

Animals↗

Real-time ultrasonographic assessment of antroduodenal motility after ingestion of solid and liquid meals by patients with functional dyspepsia.

BACKGROUND AND AIMS: Although antroduodenal motility has usually been studied by using manometric or scintigraphic methods, ultrasonography is an established, non-invasive method to evaluate duodenogastric motility. We used ultrasonography to evaluate gastric motility in patients with functional dyspepsia. METHODS: Sixty-four patients with functional dyspepsia and 36 asymptomatic healthy subjects were given liquid and solid test meals. We investigated the gastric emptying rate, motility index, and duodenogastric reflux for the liquid meal and gastric emptying time, half-emptying time, and motility index for the solid meal. RESULTS: After the liquid meal, the gastric emptying rate and motility index were significantly lower and the duodenogastric reflux was significantly higher in functional dyspepsia patients than in healthy subjects. After the solid meal, gastric emptying time, half-emptying time and the motility index were significantly lower in the patients than in the healthy subjects. Delayed gastric emptying of both meals occurred in only 20.3% of patients. Delayed emptying of the liquid or solid meal occurred in 62.5% of patients. In both groups, gastric emptying time of the solid meal was positively correlated with the motility index at 15 min post-ingestion. CONCLUSION: In functional dyspepsia patients, delayed gastric emptying of a solid meal was related to antral hypomotility during the early postprandial phase. Ultrasonographic assessment of gastric motility in both liquid and solid meals may provide a better understanding of the pathogenesis of functional dyspepsia.

Adult↗

Negative association between Helicobacter pylori infection and reflux esophagitis in older patients: case-control study in Japan.

BACKGROUND: Recent studies have clarified a close association between H. pylori infection and gastritis, peptic ulcer disease, and gastric cancer, but there is little information concerning the relationship between H. pylori infection and reflux esophagitis (RE). We investigated the relationship between H. pylori, RE, and corpus gastritis. SUBJECTS AND METHODS: Ninety-five patients with RE and 190 sex- and age-matched asymptomatic healthy controls demonstrating no localized lesions in the upper GI tract were studied and evaluated for H. pylori infection, histologic gastritis, serum gastrin, and pepsinogens (PGs). RESULTS: H. pylori infection was significantly lower in RE patients than in asymptomatic controls (41% vs. 76%, p <.01). Histologic gastritis of both the antrum and corpus was significantly less frequent (antrum; p <.01, corpus; p <. 01), and serum levels of PGI and the PG I/II ratio were significantly higher in RE patients than in controls (PGI; p <.05, PG I/II ratio; p <.01). When the subjects were divided into two age groups (59 years of age and younger and 60 years of age and older), a significant difference was found only among patients over 60 years of age (29% vs. 85%, p <.01). Among subjects in this age group, gastritis in both the antrum and corpus were significantly milder in RE patients than in controls. Although the prevalence of H. pylori infection was similar between the two groups of patients under 59 years of age, corpus gastritis was significantly milder in patients than in controls (p <.05). CONCLUSIONS: A significantly low prevalence of H. pylori infection was found in RE patients over 60 years of age but not in those under 59 in comparison with sex- and age-matched controls. The relative lack of corpus gastritis might play a role in the pathogenesis of RE in our population through preservation of the acid secretion area.

Age Factors↗

Factors that affect results of the 13C urea breath test in Japanese patients.

BACKGROUND: The 13C urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Our objective was to investigate the accuracy of the UBT in Japanese patients and the association of UBT values with histological findings. MATERIALS AND METHODS: A total of 169 consecutive patients were studied by endoscopy with histology, by serology with IgG antibody and test serum pepsinogen (PG), and by UBT. The association between UBT values and histological findings and the PG I / II ratio were analyzed in H. pylori-positive patients. RESULTS: Of 169 Japanese patients, 135 were H. pylori-positive on both histology and serology analysis, 27 were H. pylori-negative on both histology and serology analysis, and 7 patients showed differing results. Using a cutoff value of 2.5 per thousand, test sensitivity was 100%, while specificity was 96%. Among the 135 H. pylori-positive patients, a significant relation was observed between UBT value and H. pylori colonization density of the corpus and antrum, neutrophil activity of the antrum, atrophy, and intestinal metaplasia of the corpus in the H. pylori-positive patients. Also, UBT values correlated with the PG I /II ratio. In multivariate analysis, the PG I /II ratio was the most important factor related to UBT values (odds ration [OR], 4. 99; 95% confidence interval, 1.60-15.55). CONCLUSIONS: The UBT is an accurate method for detecting H. pylori infection in the Japanese population, which shows a high prevalence of atrophic gastritis. Values are affected by H. pylori infection and by the severity of atrophic gastritis.

Adolescent↗

Helicobacter pylori infection is a major risk factor for gastric carcinoma in young patients.

BACKGROUND: Helicobacter pylori has been established as a risk factor for gastric carcinoma (GCa). Since before the discovery of H. pylori, atrophic gastritis and intestinal metaplasia have been linked to GCa, especially the intestinal-type tumor. The prevalence of H. pylori infection and atrophic gastritis increase with age. Thus, analysis of H. pylori infection in young patients with GCa could help clarify the role of this bacterium in the development of GCa. Accordingly, we investigated the relationship between H. pylori infection, GCa, and histologic gastritis in patients less than 30 years old. METHODS: Fifty GCa patients less than 30 years (mean, 26.4 years) and 100 sex- and age-matched controls (mean, 26.8 years) were examined for the presence of H. pylori infection and histologic gastritis. RESULTS: The prevalence of H. pylori infection was significantly higher in GCa patients than in controls (94% versus 40%, P < 0.01). Its prevalence was not associated with tumor location, tumor stage, or histologic type. Gastritis, atrophy, and intestinal metaplasia significantly increased the risk of GCa. By means of multiple logistic regression analysis, the odds ratio for the risk of GCa in H. pylori-positive subjects was found to be 23.5 (95% confidence interval, 6.84-80.7). CONCLUSIONS: We confirmed a strong association between H. pylori infection and GCa in young patients. Along with H. pylori infection, histologic gastritis might play an important role in the pathogenesis of GCa in these patients.

Adult↗

Helicobacter pylori and dyspepsia: a population-based study of the organism and host.

OBJECTIVE: The role of Helicobacter pylori (HP) infection in dyspepsia in the absence of peptic ulcer remains controversial. Specific attributes of the organism or the host response may be important. We aimed to determine whether HP infection overall, CagA status, serum gastrin, or serum pepsinogen levels are associated with dyspepsia in the community. METHODS: A self-report bowel disease questionnaire was mailed to a random sample of Olmsted County, Minnesota residents, aged 20-50 yr. All respondents who reported symptoms of dyspepsia or irritable bowel syndrome (cases) and all respondents without significant GI symptoms (controls) were invited to participate (n = 260). They were each assessed by a physician and their medical records reviewed. Serum was obtained to measure HP and CagA antibodies, pepsinogen I and II levels, and basal serum gastrin using validated assays. RESULTS: Of the 148 (57%) subjects who agreed to participate, 36 had dyspepsia (17 had ulcer-like dyspepsia), 35 had irritable bowel syndrome (IBS) without dyspepsia, and 77 were asymptomatic. The proportion who were seropositive for HP were 17% in dyspepsia (24% in ulcer-like dyspepsia), 20% in IBS, and 12% in asymptomatic controls. HP was not associated with dyspepsia, ulcer-like dyspepsia, or IBS after adjusting for age. Pepsinogen levels and serum gastrin were not associated with any of the conditions studied. However, CagA antibody positivity was associated with IBS (p < 0.05), and a borderline statistically significant association with dyspepsia was detected (p = 0.08). CONCLUSIONS: In this community, HP infection overall does not seem to explain dyspepsia, although the role of CagA-positive HP strains deserve further study.

Adult↗

Growth characteristics of rectal carcinoid tumors.

PURPOSE: Tissue growth depends on both cell proliferation and cell death. This study was designed to examine the growth characteristics of rectal carcinoid tumors. METHODS: Fifty rectal carcinoid tumors were studied clinicopathologically and experimentally. Expression of Ki-67, TGF-alpha, p53, and bcl-2 was examined immunohistochemically, and apoptotic cells were identified by the in situ DNA nick end labeling method. EGF receptor expression was examined by a colorimetric in situ mRNA hybridization technique. RESULTS: The median Ki-67 labeling index (LI) in all lesions was 0.62 +/- 0.59%. Ki-67 LI was significantly (p < 0.01) higher in lesions larger than 5 mm than in lesions smaller than 5 mm. TGF-alpha was expressed more frequently (p < 0.01) in lesions larger than 5 mm (100%) than in lesions smaller than 5 mm (65.2%). Ki-67 LI was significantly (p < 0. 05) higher in lesions with TGF-alpha expression than in lesions without TGF-alpha expression. The in situ hybridization revealed EGF receptor expression in all 46 lesions with intact mRNA (100%), and coexpression of TGF-alpha and EGF receptor was found in 39 of the 46 (84.8%) lesions. The median apoptotic index (AI) in all lesions was 0.15 +/- 0.12%. AI has increased with tumor size and was significantly (p < 0.05) higher in lesions with a higher Ki-67 LI than in lesions with a lower Ki-67 LI. p53 protein was detected in only 1 patient who had liver metastases, and the gene mutation was confirmed by polymerase chain reaction and single-strand conformation polymorphism analysis. bcl-2 expression was absent in all lesions. CONCLUSIONS: The Ki-67 LI indicated a low cellular proliferative activity in rectal carcinoid tumors. AI was very low, and was significantly correlated with proliferative rate. Inhibition of apoptosis by mutated p53 or bcl-2 may not have occurred in most of these tumors. TGF-alpha/EGF receptor autocrine mechanisms may play a possible role in tumor growth, and the cellular proliferative activity may increase as tumors grow larger.

Apoptosis↗

Expression of cell cycle regulators and growth factor/receptor systems in gastric carcinoma in young adults: association with Helicobacter pylori infection.

We studied the expression of cell cycle regulators and growth factor-receptor systems in gastric carcinoma in young adults and tried to clarify the specific alterations associated with H. pylori. We studied 33 young patients (18-29 years old, mean age 26.4) with gastric carcinoma. The patients were classified into two groups according to the degree of atrophic gastritis. Then we examined the expression of p53, cripto, cyclin-E, c-met, c-erbB2 and TGF-alpha immunohistochemically and compared the results between the two groups. The results were compared with 66 sex-, tumor histology-, and depth-matched elder controls (36-86 years old, mean age 64.0). H. pylori was judged by Giemsa staining. Seventeen patients had atrophic changes in the corpus (Group A), while 16 showed superficial gastritis or normal mucosa (Group S). All 17 patients of Group A showed H. pylori infection, while the 3 of the 16 members of Group S did not have H. pylori. p53 overexpression was observed more frequently in Group S (88%) than in Group A (41%, p<0.05). In the 3 patients without H. pylori infection, all carcinoma specimens showed p53 overexpression. Overexpression of cyclin-E was detected in 4 patients from Group S. On the other hand, cripto was observed more frequently in Group A than in Group S. No obvious differences were observed in c-erbB2, TGF-alpha and c-met expression. Overall, p53 overexpression was detected more frequently in younger than in older patients, whereas cripto expression was less detected. These results suggest that p53 and cyclin-E may act in an H. pylori-independent or -adjunctive manner for gastric carcinogenesis. Cripto expression might be correlated tightly with H. pylori infection.

Adolescent↗

Clinical significance of MUC1 and E-cadherin expression, cellular proliferation, and angiogenesis at the deepest invasive portion of colorectal cancer.

We examined MUC1 and E-cadherin expression, cellular proliferation, and tumor vascularization at the deepest invasive portion of colorectal cancer in relation to prognosis. One hundred and ten surgically resected specimens of advanced colorectal carcinoma were studied. E-cadherin and MUC1 expression and Ki-67 labeling index (Ki-67 LI) were examined immunohistochemically at the site of deepest tumor invasion. Tumor vascularization was also examined immunohistochemically using anti-CD34 antibody to determine the microvessel count (MVC). In curative resection, patients with a high Ki-67 LI, reduced E-cadherin expression, MUC1-positive and high MVC lesion showed a significantly poorer prognosis than those with a low Ki-67 LI, E-cadherin normal, MUC1-negative and low MVC lesion, respectively. Furthermore, patients with both a high Ki-67 LI and MVC lesion showed a significantly poorer prognosis than those with other Ki-67 LI and MVC relations. Patients with both a MUC1-positive and E-cadherin reduced lesion showed a significantly poorer prognosis than those with both a MUC1-negative and E-cadherin normal lesion. The significant risk factors in order of poorer prognosis by the multivariate analysis among these factors including routinely used clinicopathologic factors were the high MVC, E-cadherin reduced expression, and lymph node metastasis. These findings indicate a high MVC at the site of deepest tumor invasion to be the most important predictor of colorectal cancer prognosis among the factors studied here.

Biomarkers, Tumor↗

Pit pattern diagnosis of early colorectal carcinoma by magnifying colonoscopy: clinical and histological implications.

The relation between subclassification of V type pit pattern and histopathologic features, particularly, in regards to the invasion depth, was examined in 75 cases of early colorectal carcinoma. After we classified two grades (VA, VN) of V type pit pattern, we subclassified VN type pit pattern into three subtypes (Grade A, B, and C) according to the degree of appearance of VN pit pattern. V type pit pattern subclassification was diagnosed with use of a magnifying colonoscope. There were 37 VA type lesions, 8 VN.Grade A type, 16 VN.Grade B type, and 14 VN.Grade C type lesions. The incidence of submucosal massive invasion (sm2, sm3) rates was 5 (14%) of the 37 VA type lesions, 3 (38%) of the 8 VN.Grade A type, 15 (94%) of the 16 VN.Grade B type and 14 (100%) of the 14 VN.Grade C type lesions, respectively. The incidence of desmoplastic reaction (++) levels in VN.Grade B and C type lesions was significantly higher than that in VA type lesions (P<0.01), and that in VN.Grade C type lesions was significantly higher than that in VN.Grade A type lesions (P<0.05). The incidence of pit disorder or destruction (+) and (++) levels in VN.Grade B and C type lesions was significantly higher than that in VA type lesions (P<0.01), and that in VN.Grade C type lesions was significantly higher than that in VN.Grade A type lesions (P<0.01). The incidence of high grade carcinoma in VN.Grade B and C type lesions was significantly higher than that in VA type lesions (P<0.01), and that in VN.Grade C type lesions was significantly higher than that in VN.Grade A type lesions (P<0.05). These findings indicate that V type pit pattern subclassification, including our new subtype, is useful for predicting the detail invasion depth of early colorectal carcinoma. These V pit pattern subtypes are based on the degrees of desmoplastic reaction, pit disorder or destruction, and histologic grade of carcinoma.

Carcinoma↗

Evaluation of flash echo imaging of the canine gastrointestinal tract.

Although it is important to assess gastrointestinal blood flow, no generally useful, noninvasive assessment method has been established. Harmonic flash echo imaging, which is an intermittent second harmonic imaging technique, has recently become available to evaluate blood flow. We investigated the usefulness of harmonic flash echo imaging in the assessment of the gastrointestinal tract, and we used this technique to study the effect of nicotine on small bowel blood flow. Harmonic flash echo imaging was performed at the beginning of intravenous injection of a contrast agent. It was also performed on the small bowel immediately before and 10 min after nicotine administration to evaluate blood flow. Gastric and small bowel walls were clearly enhanced on the primary images. Small bowel enhancement, which is regarded as transmural blood flow, significantly decreased after nicotine administration. Harmonic flash echo imaging appears to be useful in the assessment of the transmural blood flow in the gastrointestinal wall.

Animals↗

Detailed colonoscopy for detecting early superficial carcinoma: recent developments.

Early superficial colorectal carcinoma (CRC) has been commonly detected by routine colonoscopic examination in Japan. A series of 769 early CRCs and 4821 adenomas were diagnosed by colonoscopy at Hiroshima University Medical Hospital between 1991 and 1998. Of early CRCs, macroscopically superficial early CRCs accounted for 209 lesions (28%). Among 5590 lesions of adenomas and carcinomas, depressed-type lesions showed a significantly higher malignant potential for cancerous and submucosal invasion than elevated lesions (polypoid, IIa-type lesions, and G-LST). As one of the quantitative examinations for early CRC, pit pattern observed by magnifying video-colonoscopy was useful. We performed magnifying observations for 265 lesions of colorectal neoplasias using Kudo's pit pattern classification for 2 years. Depressed-type lesions characterized the Ills and V pit patterns, and elevated lesions characterized the III(L) pit pattern. The incidence of cancer was significantly higher in lesions with IIIs and V pit patterns. Furthermore, the V(N) pit pattern was considered a significant indicator of submucosal invasion. These results indicated that superficial early CRC could be considered to constitute about one-third of all early CRCs. Of them, the depressed-type lesions showed a significantly higher malignant potential than elevated lesions. Pit pattern observation by magnifying videocolonoscopy is useful for predicting the histology/invasion depth of early CRC.

Adenomatous Polyps↗

Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8.

The expression of interleukin 8 (IL-8) by human gastric carcinomas directly correlates with tumor vascularity and disease progression. To determine whether IL-8 can act in an autocrine manner to regulate the expression of other disease-progression genes, we examined the expression of IL-8 receptors IL-8RA (CXCR1) and IL-8RB (CXCR2) in six different human gastric carcinoma cell lines and 38 surgical specimens of human gastric carcinomas. All of the gastric carcinoma cell lines expressed mRNA and protein for IL-8RA and IL-8RB protein. In all surgical specimens, the majority of the tumor cells and small vessel endothelial cells stained positive for IL-8RA and IL-8RB protein. In vitro treatment of human gastric cancer MKN-1 cells with exogenous IL-8 enhanced the expression of epidermal growth factor receptor, type IV collagenase (metalloproteinase-9), vascular endothelial growth factor, and IL-8 mRNA. In contrast, treatment with exogenous IL-8 decreased expression of E-cadherin mRNA. IL-8 treatment increased invasive capacity of MKN-1 cells, which was associated with activity of metalloproteinase-9. Collectively, these results demonstrate that human gastric carcinoma cells express receptors for IL-8 and that IL-8 may play a role in the progressive growth of human gastric carcinoma by autocrine/paracrine mechanisms.

Cell Membrane↗

Laparoscopic resection of submucosal gastric tumors.

In order to elucidate the efficacy in gastric surgery, we evaluated seven resected cases of a submucosal gastric tumor in which laparoscopic techniques were used. The patients consisted of 1 man and 6 women. The tumors were located in the upper, middle, and lower third of the stomach in 4, 1, and 2 cases, respectively. Three tumors were located mainly on the anterior gastric wall, 2 were on the posterior wall, and 2 were on the lesser curvature. The resected tumor size averaged 3.2 x 2.6 cm. The tumors were classified as intraluminal type (4 cases) and the extraluminal type (3 cases) according to the classification of growth type. A histopathological examination identified 4 leiomyomas, 1 leiomyosarcoma, and 4 smooth muscle tumors of indeterminate malignant potential. After a tumor resection, no recurrence of the lesions occurred during the postoperative follow-up. An extraluminal growing tumor was easily resected by the laparoscopic method without any additional procedures, and this therefore seemed to be a good indication for the laparoscopic method. In contrast, an intraluminal tumor was found to be more difficult to resect using the laparoscopic method without a companion method, e.g., intraoperative endoscopy, because of the difficulties in the detection and resection of the tumor from the serosal side. A more efficient technique must therefore be developed for this type of tumor.

Aged↗

Overexpression of human telomerase RNA is an early event in oesophageal carcinogenesis.

Telomerase, the ribonucleoprotein enzyme that elongates telomeres, is repressed in normal human somatic cells but is reactivated during tumour progression. The purpose of this study was to investigate the localization of human telomerase RNA (hTR) expression in human oesophageal dysplasia and cancer by using in situ mRNA hybridization (ISH) with avidin-biotin staining. Ki-67 immunoreactivity was also examined. We analysed 51 squamous cell carcinomas, 9 dysplasias and 60 normal mucosae. The integrity of the mRNA in each sample was verified by using a poly d(T)20 probe. Seventy-six samples (63%) showed no mRNA degradation; these included 30 carcinomas, 7 dysplasias and 39 normal mucosae. At the single-cell level, high levels of hTR expression were found in the cytoplasm and especially in the nucleus. Most (>90%) cancer cells demonstrated high levels of hTR expression in 29 (97%) of the 30 tumours. Most dysplastic cells also showed high levels of hTR in all 7 dysplastic cases. In all 39 normal mucosae, most basal cells indicated high levels of hTR expression, which were also seen in infiltrating lymphocytes. The distribution of hTR-expressing cells was similar to that of Ki-67-positive cells. These data suggest that overexpression of hTR may be correlated with the proliferative activity that defined by Ki-67 immunoreactivity and is an early event in carcinogenesis of the oesophagus.

Esophageal Neoplasms↗

Transfection of interleukin-8 increases angiogenesis and tumorigenesis of human gastric carcinoma cells in nude mice.

The growth and spread of tumour cells depends on adequate vasculature. We have previously reported that the expression of interleukin-8 (IL-8) directly correlates with the vascularity of human gastric carcinomas. To provide evidence for a causal role of IL-8 in angiogenesis and tumorigenicity of human gastric cancer, we used the lipofectin method to stably transfect the human TMK-1 gastric carcinoma cells (low endogenous IL-8) with an IL-8 expression vector or control vector. Transfection with IL-8 did not affect the proliferation of cultured cells, yet the culture supernatants of the transfected (but not control) cells stimulated proliferation of human umbilical vein endothelial cells. The IL-8-transfected and control cells were injected into the gastric wall of nude mice. IL-8-transfected cells produced rapidly growing, highly vascular neoplasms as compared to control cells. These results provide direct evidence for the role of IL-8 in the angiogenesis and tumorigenicity of human gastric carcinomas.

Animals↗