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Biomedical subjects

M Sowa

Publications and source records attributed to M Sowa.

At least 19 recordsLinked to original sources
PubMed2006

Combined administration of PHCCC, a positive allosteric modulator of mGlu4 receptors and ACPT-I, mGlu III receptor agonist evokes antidepressant-like effects in rats.

Numerous pharmacological data indicate involvement of glutamate, the major excitatory neurotransmitter in the brain, in the pathophysiology of several neuropsychiatric disorders. It was shown in the preclinical studies that compounds which can reduce the excess of glutamate release (for example group III metabotropic receptors agonists) possess potential therapeutic properties. Thus we focused our interests on (-)-N-phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide (PHCCC), which is a positive allosteric modulator of mGlu4 receptor. We examined the potential antidepressant-like activity of PHCCC after injection into the brain ventricles alone, or together with (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-I), a nonselective group III mGlu receptor agonist, using the forced swimming test (FST) in rats. We found that ACPT-I induced a dose dependent antidepressant-like effect in FST, which was blocked by an antagonist of group III mGlu receptors (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). PHCCC injected intracerebroventricular was not effective, however when the compound was administered together with non-effective dose of ACPT-I, a profound antidepressant-like activity in FST was demonstrated. This effect was reversed by CPPG, group III mGlu receptors antagonist. Results of our studies indicate that a combined administration positive allosteric modulation of mGlu4 receptor and agonists of group III mGlu receptors may be a promising target in the future treatment of depressive disorder.

Allosteric Site↗
PubMed2001

Visualization of cutaneous hemoglobin oxygenation and skin hydration using near-infrared spectroscopic imaging.

BACKGROUND/AIMS: The visualization of skin hemodynamics and tissue water content has important implications in a number of areas of dermatology, plastic surgery, and clinical skin evaluation. The aim of this study was to develop instrumentation and techniques for infrared spectroscopic imaging, and to evaluate whether they can be used to make objective assessments of skin health, perhaps even before clinical signs are evident. METHODS: A liquid-crystal tunable filter was mounted on the front of the objective lens of an infrared-sensitive charge-coupled device digital camera. Sets of narrow-band images of skin were acquired in vivo at wavelength intervals of 10 nm from 650 to 1050 nm, under computer control. The data processing techniques used to extract interpretable clinical information from the raw image sets included normalization, ratios, and multivariate analysis. RESULTS: To highlight the capabilities of these techniques, results are presented of two studies that generated spectroscopic images. One examined a volunteer's forearm subjected to short interruptions of blood flow, and the other followed changes in a skin flap elevated on a rat model. The data sets were processed in different ways to determine several skin and blood parameters, in particular hemoglobin oxygen saturation, blood volume, and skin hydration. Variations in these parameters were followed non-invasively as a function of time and location to study the skin's response to blood flow changes, and to predict the viability of the skin. CONCLUSION: Near-infrared reflectance spectroscopic imaging is demonstrated to be a powerful augmentation to the standard clinical assessment of skin.

Animals↗
PubMed2001

A combination analysis of p53 and p21 in gastric carcinoma as a strong indicator for prognosis.

We studied p53 and p21 expression simultaneously in gastric carcinoma tissues to investigate the clinical significance of p53-p21 pathway in this disease. One hundred sixty-four primary gastric carcinoma specimens were immunohistochemically stained for p53 and p21 protein, and clinicopathological features of the cases were examined. P53 was stained negatively, while p21 was stained positively in each normal stomach epithelium. P53, and p21 positive staining was observed in 82 (50%) and 61 (37.2%) tumors, respectively. Unexpectingly, no correlation was found between p53 and p21 staining status. Tumors demonstrating preserved p53-p21 pathway [p53(-)/p21(+)], observed in 20.1% of the tumors, displayed less aggressive characteristics, and no recurrent disease after curative resection. While tumors demonstrating disrupted p53-p21 pathway [p53(+)/p21(-)], observed in 32.9% of the tumors, displayed significantly more aggressive characteristics, poorer survival and higher recurrence rate than the tumors demonstrating other staining patterns. P53-p21 pathway was widely altered in gastric carcinomas. The combined evaluation of p53 and p21 expression in gastric carcinoma tissues is suggested to have clinical importance by indicating not only the malignant potential of each tumor, but also the prognosis of this disease.

Adenocarcinoma↗
PubMed2001

Proliferating cell nuclear antigen labeling index and p53 expression predict outcome for breast cancer patients with four or more lymph node metastases.

In general, extensive lymph node metastasis indicates poor prognosis in breast cancer. Nevertheless, some patients with this condition survive for a long time without recurrent disease. This study involved 112 breast cancer patients with four or more lymph node metastases and without distant metastasis who underwent surgery. p53 expression was associated with shorter overall and disease-free survival. High PCNA labeling index was associated with shorter overall disease-free survival. p53-negative and low-PCNA patients survived much longer than p53-positive and high-PCNA patients. This study showed that p53-negative or low-PCNA index patients have relatively good prognoses despite extensive lymph node metastasis.

Adult↗
PubMed2000

Forskolin and phorbol ester have opposite effects on the expression of mucin-associated sialyl-Lewis(a) in pancreatic cancer cells.

The carbohydrate antigen sialyl-Lewis(a) is important to pancreatic tumour biology because the circulating antigen is used in serological tests for malignancy and because cell surface antigen is involved in tumour cell binding to the endothelial adhesion molecule, E-selectin, in extravasation. In this study, we examined the effects of the adenylyl cyclase activator, forskolin, and the diacylglycerol analogue, phorbol 12-myristate 13-acetate (PMA), on the expression and release of sialyl-Lewis(a) in human pancreatic cancer cells. Increases in the release of sialyl-Lewis(a) from SW1990 cells produced by forskolin and PMA were associated with increases in the activities of protein kinases A and C, respectively, and could be blocked by inhibitors specific for these enzymes. Immunoprecipitation experiments showed that sialyl-Lewis(a) was associated with MUC1 mucin. Forskolin also increased the cellular content of antigen and MUC1 mRNA. Actinomycin D and a protein kinase A inhibitor, H8, blocked these effects. In contrast, PMA reduced cellular antigen and MUC1 mRNA levels, although it produced a temporary increase in release of the antigen. The effects of PMA were blocked by the protein kinase C inhibitor, H7. PMA also reduced cell binding to the adhesion molecule E-selectin. In summary, PKA and PKC alter cell MUC1-associated sialyl-Lewis(a) in opposite directions. These changes may have clinical utility in the diagnosis of pancreatic cancer and the prevention of metastases.

Blotting, Western↗
PubMed2000

Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats.

Proliferation and activation of hepatic stellate cells (HSCs) are critical steps for the development of postnecrotic fibrosis in the liver. The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP-470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl(4))- and dimethylnitrosamine-induced hepatic fibrosis were used for an in vivo study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg/kg body weight of TNP-470. In CCl(4)-induced fibrosis, factor VIII-related antigen-positive blood vessels, desmin-, or alpha-smooth muscle actin (alphaSMA)-positive mesenchymal cells, bromodeoxyuridine (BrdU)-positive mesenchymal cells also decreased in number by treatment with TNP-470. In in vitro experiments, a supplement of 1,000 ng/mL TNP-470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and/or presence of platelet-derived growth factor (PDGF). Expression of HSC activation markers, i.e., alphaSMA and PDGF receptor beta, was also suppressed. The present results indicate that TNP-470 inhibits HSC proliferation by blocking the cell-cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect.

Actins↗
PubMed2000

[Genome analyses for precancerous lesions in the gastrointestinal tract].

We herein summarize the reports on genetic changes in precancerous lesions in the gastrointestinal tract. It has been reported that with esophageal lesions such as dysplasia and Barrett's esophagus there is a high frequency of p53 mutations. Among gastric lesions, some cases of chronic atrophic gastritis have been shown to harbor K-ras mutations. p53 and APC mutations in intestinal metaplasia have also been demonstrated, as have APC mutations in flat adenomas. With colorectal lesions, it has been reported that K-ras, DCC, p53 mutations commonly occur while APC mutations are also seen in cases of adenoma-carcinoma. p53 and K-ras mutations have been demonstrated with serrated adenoma, and K-ras mutations with hyperplastic polyps APC mutations in familial polyposis coli, LKB1 mutations in Peutz-Jeghers syndrome, and SMAD4/DPC4 mutations in juvenile polyposis syndrome have been found. Besides these genes, other genetic changes likely occur in carcinogenesis among those with hereditary diseases. K-ras mutations in aberrant crypt foci and hMSH2 mutations in ulcerative colitis have been found. Research into the genetic changes associated with cancerous lesions should lead to the development of early diagnosis and treatment methods for gastrointestinal cancer as well as the improved comprehension of carcinogenesis.

Adenoma↗
PubMed2000

[Current status of "low-dose cisplatin-5-FU therapy" for solid tumors (2nd report)--from a nationwide questionnaire on its adverse effects].

A nationwide questionnaire survey was carried out on low-dose cisplatin-5-FU therapy for solid malignant tumors (mostly stomach and colon cancer) regarding its antitumor as well as adverse effects. The regimen was defined as 4 weeks administration of cisplatin 2-5 mg/body, 5 days a week, which was used in 47% of 82 institutions studied. Cases were classified into an Ab regimen (86 cases) with cisplatin 3-5 mg/body, and a Bb regimen (122 cases) with cisplatin 6-30 mg (mostly 10 mg)/body, both of which were given 5-FU 300-500 mg/body daily. The antitumor effect (CR + PR) was shown to be slightly higher in the Bb regimen than in the Ab regimen, and was 35% overall. Very few adverse effects appeared with either regimen for mostly major digestive, hepatic and renal functions, except for myelodepressions (leucopenia and thrombocytopenia), which were more than grade 3 in only a few percent with the Ab regimen, and a little more than 10% with the Bb regimen. The advantages and disadvantages of the A/Bb regimens appeared to be counter-balanced in terms of their antitumor and adverse effects. Most institutions using the Ab regimen favored repeating the regimen cycle as much as possible. Those using more than 6 cycles accounted for about 20% of hospitals.

Antimetabolites, Antineoplastic↗
PubMed1999

Matrix metalloproteinase-1 expression is a prognostic factor for patients with advanced gastric cancer.

Proteolytic activity of cancer cells is an important factor in metastasis. This study examined the relationship between MMP-1 expression of gastric cancer cells and peritoneal metastasis. MMP-1 expression was found in 76/103 (75.2%) cases examined and was significantly associated with both peritoneal metastasis and lymph node metastasis (p<0.05, respectively). The prognosis of patients with MMP-1 positive tumor was significantly worse than that of patients with MMP-1 negative tumor (p<0.05). These findings suggested that MMP-1 might be a prognostic factor in case of advanced gastric cancer and might be useful in determining whether or not adjuvant therapy was indicated for patients at high risk of peritoneal recurrence.

Adult↗
PubMed1999

[Low-dose FP therapy for advanced and recurrent gastric cancer].

Continuous infusion of 5-FU and low-dose CDDP infusion (low-dose FP therapy) is one of the effective combination chemotherapies for advanced and recurrent gastric cancer. Several studies have reported low-dose FP therapy showed high response rates (40-50%) and a low incidence of toxicities. There was a positive correlation between antitumor effect and survival time on neoadjuvant chemotherapy for advanced gastric cancer. It still may be necessary to improve quality of life by changing the regimen of low-dose FP therapy because patients require hospitalization for the therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Serum CA 125 level as a predictor of peritoneal dissemination in patients with gastric carcinoma.

BACKGROUND: Prediction of peritoneal dissemination is very difficult using current diagnostic tools such as computed tomography, ultrasonography, or various tumor markers. The predictive value of serum CA 125 levels for peritoneal metastasis from gastric carcinoma was studied. METHODS: The sera from 384 patients with gastric carcinoma were measured for CA 125 titer using an immunoradiometric assay. Carcinoembryonic antigen, carbohydrate antigen 19-9, and sialyl-Tn antigen were measured in the same samples. RESULTS: The serum CA 125 level was elevated according to the degree of peritoneal dissemination. The reference value for peritoneal dissemination was determined to be 35 U/mL, resulting in a sensitivity of 39.4%, specificity of 95.7%, and diagnostic accuracy of 90.8%. The diagnostic ability was more reliable than the other imaging modalities including computed tomography and ultrasonography and the other useful tumor markers for gastric carcinoma. The serum CA 125 level was elevated after gastrectomy for approximately 2 months, most likely due to the continuous inflammation of the peritoneum and lost predictive significance for peritoneal dissemination during this period. CONCLUSIONS: Measurement of the serum CA 125 titer may be a powerful predictor of peritoneal metastases in patients with gastric carcinoma.

Adult↗
PubMed1998

Changes in tumor marker levels as a predictor of chemotherapeutic effect in patients with gastric carcinoma.

BACKGROUND: Evaluating chemotherapeutic effect in patients with gastric carcinoma sometimes is difficult. The authors investigated whether changes in the serum levels of three tumor markers can be used to predict the clinical outcome after chemotherapy. METHODS: Thirty patients with advanced and recurrent gastric carcinoma were treated with continuous 5-fluorouracil and low dose cisplatin for 4 weeks. Thirteen patients were treated neoadjuvantly prior to gastrectomy. The serum levels of carcinoembryonic antigen, carbohydrate antigen 19-9, and sialyl-Tn antigen were measured prior to and after chemotherapy. Responders were defined as those in whom abnormal serum levels of all three markers decreased to at least 50% of the pretreatment values and remained stable for at least 1 month. RESULTS: The tumor markers could be evaluated in 27 of 30 patients (90%). The median duration of survival for the 15 responders and 12 nonresponders was 17 months and 6 months, respectively. There was a significant difference in the median duration of survival between the responders and nonresponders using the log rank test (P=0.0005). In the patients who received neoadjuvant therapy, the eight responders had a significantly longer survival period than did the three nonresponders (P=0.018). Seven of the eight responders showed evidence of tumor destruction histologically whereas none of the three nonresponders did. CONCLUSIONS: Changes in the serum levels of these tumor markers after chemotherapy may be an excellent prognostic indicator for patients with gastric carcinoma.

Adult↗
PubMed1998

Diagnostic potential and pitfalls of ultrasound-guided fine-needle aspiration cytology for breast lesions.

Ultrasound (US)-guided fine-needle aspiration cytology (FNAC) is now widely accepted as a diagnostic procedure for breast lesions. Along with its advantages, US-guided FNAC also has some pitfalls. The recognition of these pitfalls for this procedure is extremely important for the strict management of the disease. We retrospectively investigated the diagnostic potential and pitfalls of US-guided FNAC in the diagnosis of breast lesions. This study consisted of 348 aspirated samples from 274 breast tumors. The rate of sufficient aspirates was 74% after a single aspiration, while sufficient materials were finally obtained from 93% of the tumors by repeated aspirations. The rate was lower in tumors measuring less than 10 mm in diameter (62%), and in sclerosing adenosis (25%). The sensitivity of FNAC was 65%, the specificity was 75%, the border diagnosis rate was 18%, and the positive predictive value was 92%. The false-negative rate was higher in noninvasive carcinoma (45%). The border diagnosis rate was also higher in scirrhous carcinoma (29%). There were also five false-positive cases. Limited to nonpalpable lesions, the sufficient aspirates rate was 70% and the accuracy was 67%.

Adenocarcinoma, Scirrhous↗
PubMed1998

p53 protein overexpression as a predictor of the response to chemotherapy in gastric cancer.

This study was performed to evaluate p53 overexpression as a predictor of the response to chemotherapy of patients with gastric cancer. The subjects comprised 20 patients with Stage IV gastric cancer and three with locally recurrent lesions, all of whom were treated with 5-fluorouracil (5-FU) plus cisplatin (CDDP) for 4 weeks. Of the total 23 patients there were 10 responders; 2 showing complete response (CR) and 8, partial response (PR). Specimens obtained by endoscopic biopsy were immunohistochemically stained using anti-p53 protein and bcl-2 protein antibody. Of the 10 responders, 7 demonstrated negative p53 staining, and of the 13 nonresponders, 11 demonstrated positive p53 staining (P = 0.013). Tissue from 3 of the responders and 7 of the nonresponders that stained for bcl-2 were positive prior to chemotherapy; however, there was no association between bcl-2 staining and chemotherapeutic effect. In conclusion, immunohistochemical identification of p53 in pretreatment tissue may represent a useful predictor for chemotherapeutic outcome in patients with gastric cancer.

Adult↗
PubMed1998

Establishment of lymph node metastatic model for human gastric cancer in nude mice and analysis of factors associated with metastasis.

The actual mechanisms responsible for lymph node metastasis in gastric cancer are still unclear. To investigate the mechanisms of lymph node metastasis in gastric cancer, we established a lymph node metastatic model for human scirrhous gastric carcinoma. Lymph node metastasis had frequently developed after orthotopic implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line, OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the different characteristics including binding ability, migratory capacity and immunoresponses induced by the cell surface molecules of these two cell lines. The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were significantly greater than those of OCUM-2M cells. On flow cytometric analysis, both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but neither cell line expressed HLA-II (0.0 and 0.0%), B7-1 (0.0 and 0.0%) or B7-2 (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays, both of which were significantly decreased by the addition of anti-ICAM-1 antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN cells were significantly less than those of OCUM-2M cells, and were not affected by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph node metastasis may in turn decrease immune responses mediated through LFA-1-dependent effector cell adhesion, and that this escape from the immunosurveillance system may be one of the factors inducing lymph node metastasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN, with a high rate of lymph node metastasis. An in vivo lymph node-metastatic model with this cell line should be useful for analysing the mechanism and therapeutic approach of lymph node metastasis.

Adenocarcinoma, Scirrhous↗
PubMed1998

Adhesion polypeptides are useful for the prevention of peritoneal dissemination of gastric cancer.

We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. We previously reported the establishment of an extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both alpha2beta1 and alpha3beta1 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD, and two RGD derivatives significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination given YIGSR sequence intraperitoneally was obviously longer than that of untreated mice. The survival of mice treated with RGD was also improved, and this effect was increased using the RGD derivatives, poly(CEMA-RGDS) and CM-chitin RGDS. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM, and consequently inhibit peritoneal implantation. The peritoneal injection of adhesion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients.

Adenocarcinoma, Scirrhous↗
PubMed1998

Serum soluble interleukin-2 receptor level as a prognostic indicator in gastric cancer.

T lymphocytes, activated by interleukin 2 during an anti-tumour response, release soluble interleukin 2 receptors (sIL-2R) into the bloodstream. We analysed the prognostic value of the serum sIL-2R level in gastric cancer. Serum concentration of sIL-2R in 96 gastric cancer patients and 100 healthy control subjects' was measured by enzyme-linked immunosorbent assay. All survivors were followed for more than 50 months. Serum sIL-2R level was considered with respect to prognosis, clinicopathological factors, other tumour markers and peripheral blood cell count. Stage III and IV patients had significantly higher sIL-2R levels than lower stage patients and control subjects. Stage III and IV gastric cancer patients were divided into 'high' and 'low' slL-2R groups based upon the control subjects' serum sIL-2R mean value plus one standard deviation. The high group had a significantly worse prognosis than the low group, although clinicopathological features and treatments were similar. Multivariate analysis demonstrated that the serum sIL-2R level is an independent indicator. The sIL-2R level did not correlate with carbohydrate antigen 19-9, however it did correlate with carcinoembryonic antigen (r = 0.22) and with numbers of peripheral blood monocytes (r = 0.54). In conclusion, serum sIL-2R may predict the outcome of gastric cancer patients with stage III or IV disease.

Adult↗