Celina Tizuko Fujiyama Oshima

Depression and Anxiety in Colorectal Cancer Patients

IntroductionCancer has been seen negatively by the people that disclose fear and anxiety face to the disease closely associated with distress, aggressive treatments, and death. Colorectal cancer is one of the most prevalent cancer and few assays were developed studying depression and anxiety in patients after surgical resection of tumor and before adjuvant therapy.AimThis research aims to study the prevalence of depression and anxiety in patients with colorectal cancer before and after adjuvant chemotherapy.Patients and MethodsAfter surgical resection of colorectal cancer, 37 patients were included according to the kind of treatment: chemotherapy group (CHG) and the other one without indication of chemotherapy, the control group (CG). Questionnaires of Depression and Anxiety were done at the beginning and at the end of the treatment in the CHG (n = 19) and at the first and after 6 months of follow-up (n = 18) in the CG.ResultsNo difference on gender, age, or site was observed among the groups. Stage III tumor was more frequent in the CHG group. Mild or moderate depression was diagnosed in 31.6% of the CHG patients in the first evaluation and in 38.6% at the second one. In the CG no depression was observed in both evaluations. About the State-Trait Anxiety Inventory, the results were similar before and after chemotherapy treatment. There was a higher number of patients with moderate state or trait anxiety in the CHG when compared to the CG in both evaluations. No correlation was found about the inventories of anxiety and depression and site of tumor or stage.ConclusionAfter surgical treatment of colorectal cancer, depression and indexes of anxiety were higher in the group of patients treated with chemotherapy when compared to the control group.

Ki67 and p53 in gastrointestinal stromal tumors - GIST

CONTEXT Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor. Cellular proliferation and apoptosis is gaining importance for predicting prognosis in several cancers. OBJECTIVE To investigate the Ki67 and p53 immunostaining in GISTs. METHODS Specimens from 40 patients with GIST were assessed for immunohistochemical expression of Ki67 and p53. The tumors were divided according the risk of recurrence in two groups: I with high or intermediate risk and; II with low or very low risk. RESULTS Among the 40 patients, 21 were men, the mean age was 56 years, 16 occurred in the small intestine and 13 in the stomach, 5 in the retroperitonium, 4 in the colon or rectum and 2 in the mesenterium. Thirty two tumors were from group I and 8 from group II. Half of the patients developed recurrence, being 90% of the group I (P = 0.114). The tumor Ki67 labelling index ranged from 0.02 to 0.35 (mean level 0.12). This index was marginally higher in the group I patients with recurrence (P = 0.09) compared to the patients of the same group without recurrence. p53 staining was expressed in 65% of the GISTs. A higher frequency of p53 and Ki67 had been found in the group I tumors when compared to the other group (P = 0.022; OR = 8.00 - IC 95%: 1.32-48.65). CONCLUSION The most common site was the small intestine and 80% had a malignant potential justifying the high recurrence observed. No significant correlation was found between p53 and overall outcome of the patients. In group I patients, the evaluation Ki67LI may be a marker of prognosis. The positivity of both markers is higher among the patients with worst prognosis than in the others.

Effects of melatonin on histomorphology and on the expression of steroid receptors, VEGF, and PCNA in ovaries of pinealectomized female rats

OBJECTIVE To evaluate the effect of melatonin both on the ovaries of pinealectomized female rats through histomorphometric analysis and on steroid receptors, proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF) expression. DESIGN Experimental study. SETTING Federal University of São Paulo, Brazil. ANIMAL(S) Forty female rats. INTERVENTION(S) Forty rats were divided equally into four groups: GI-vehicle without surgery; GII--surgery without removal of the pineal gland (sham); GIII--pinealectomized with vehicle; and GIV--pinealectomized with melatonin treatment. After treatment for 3 consecutive months, the animals were killed and their ovaries removed for analysis. MAIN OUTCOME MEASURE(S) Estrogen and progesterone receptors, histologic and immunohistochemical analysis. RESULT(S) The GIII samples presented signals of proliferation on ovarian surface epithelium and interstitial cells as well as high expressions of PCNA and VEGF in those structures compared with GI, GII, and GIV. Also, the levels of progesterone receptor (fmol/g) in ovaries of GIII (250.6 ± 32.4) were significantly lower than in those of GI (429.0 ± 23,8), GII (442.3 ± 30.2), and GIV (564.1 ± 78.7). The levels of progesterone in GIII were superior to those in GI, GII, and GIV. CONCLUSION(S) Our findings suggest that melatonin may attenuate proliferation in ovarian structures and increase the number of luteal bodies as well as the levels of progesterone receptor.

Immunohistochemical expression of p16(INK4A) in normal uterine cervix, nonneoplastic epithelial lesions, and low-grade squamous intraepithelial lesions.

Objectives. In this study, the authors analyzed the immunoexpression of p16 in high-risk human papillomavirus DNA-negative normal and nonneoplastic cervical epithelia, in low-grade cervical intraepithelial neoplasia (CIN), high-grade CIN, and squamous cell carcinoma. Materials and Methods. A retrospective study, in which 58 normal cervical hysterectomy samples, 56 nonneoplastic cervical biopsies, 88 CIN 1, 33 CIN 2, 32 CIN 3, and 47 invasive squamous cell carcinoma biopsies, were evaluated for p16 immunoexpression. Human papillomavirus tests were also performed. Results. p16 immunohistochemistry seems to reveal possible different biological subgroups of lesions among morphologically similar mildly dysplastic cervical epithelia. Conclusion. Distribution patterns of p16 protein might be useful to predict different outcomes in CIN 1.

Cell proliferation and apoptosis in gastric cancer and intestinal metaplasia.

BACKGROUND Higher proliferation is commonly observed in cancer cells. Apoptosis can be a useful measure of a tumor cell kinetic. Alteration of the balance between proliferation and apoptosis is associated with cancer. AIM To study proliferation and apoptosis on gastric cancer and in intestinal metaplasia. METHODOLOGY Twenty-two samples from gastric adenocarcinomas and 22 biopsies from intestinal metaplasia were studied. The apoptotic bodies in hematoxylin-eosin slides and the expression of p53, bcl-2 and Ki67 were determined by immunohistochemistry. RESULTS The number of the apoptotic cells was higher in cancer. Ki 67LI increased from intestinal metaplasia to gastric cancer. p53 was positive in 68% of the patients with cancer, more frequently in advanced stage and negative in samples of intestinal metaplasia. Although there was no significant difference between the groups, bcl-2 was positive in 45% of gastric cancer tissue and in 68% of metaplasia. In gastric cancer patients bcl-2 was expressed in early gastric cancer more frequently than in advanced stage. CONCLUSION The positivity of bcl-2 was higher in metaplasia and probably is involved in the progression of carcinogenesis. p53 was negative in metaplasia and positive in more than half of the gastric cancer, mostly in stage IV, suggesting a late event in gastric cancer.

Immunoexpression of cyclooxygenase-1 and -2 in ulcerative colitis.

Ulcerative colitis (UC) is a disease of the colon and rectum characterized by a nonspecific chronic inflammation mediated by the concerted response of cellular and humoral events. Prostaglandins are synthesized by cyclooxygenase (COX)-1 and -2 and exhibit both pro- and anti-inflammatory activity. To evaluate COX-1 and COX-2 immunoexpression in 42 cases of UC and to correlate it with clinicopathological parameters, COX-1 and COX-2 expression was investigated by the immunohistochemistry method. Only patients with all pertinent clinical and evolutive data as well as with adequate biopsy material were included in the study. Fifteen samples of colorectal adenocarcinoma and 14 of large bowel with no histological changes were used for positive and negative controls, respectively. UC patients showed COX-1 immunoreactivity in epithelial cells in 29% of the cases and in inflammatory cells in 43%. COX-2 positivity in epithelial and inflammatory cells was found in 69% of the samples. The comparison between UC and the control groups revealed that the UC group had significantly more positive cases for COX-1 and COX-2 in inflammatory cells. Immunohistochemistry allowed the identification of COX-1 and COX-2 expression in epithelial and inflammatory cells in UC biopsies. No significant difference between COX-1 and COX-2 immunoreactivity in epithelial and inflammatory cells was observed regarding the clinicopathological parameters. COX-2 presented low expression in normal colon and high expression in colorectal adenocarcinoma. COX-2 might play a role in the pathophysiologic processes of inflammatory bowel disease and the development of neoplasia. Treatment with selective COX-2 inhibitors might be an additional option for therapy.

Biomonitoring of oral epithelial cells in smokers and non-smokers submitted to panoramic X-ray: comparison between buccal mucosa and lateral border of the tongue

The aim of the present study was to comparatively evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis, and karyorrhexis) in exfoliated oral mucosa cells from smokers and non-smokers submitted to dental X-ray using two anatomic sites: buccal mucosa and lateral border of the tongue. A total of 15 heavy smokers and 17 non-smokers were submitted to panoramic dental radiography for orthodontic reasons. Individuals had epithelial cells from cheek and lateral border of the tongue mechanically exfoliated, placed in fixative, and dropped in clean slides which were checked for the above nuclear phenotypes. The results pointed out no significant statistically differences (p > 0.05) of micronucleated oral mucosa cells before versus after X-ray exposure for both oral sites evaluated either to smokers or to non-smokers. X-ray exposure was able to increase other nuclear alterations closely related to cytotoxicity such as karrhyorexis, pyknosis, and karyolysis for two groups evaluated. Nevertheless, the most pronunciated effects were found to lateral border of the tongue of smokers. In summary, these data indicate that panoramic X-ray is able to induce cellular death in oral mucosa cells. It seems that lateral border of the tongue is more sensitive site to cytotoxic insult induced by ionizing radiation combined with continuous cigarette smoke exposure.

Evaluation of the immunoexpression of COX-1, COX-2 and p53 in Crohn's disease

BACKGROUND Crohns disease accompanied by nonspecific or idiopathic ulcerative proctocolitis corresponds to a condition called intestinal inflammatory disease. The immunoexpression of cyclooxygenase 2 (COX-2) in Crohns disease becomes more marked with progression of the disease and the presence of wild-type p53 suppresses the transcription of COX-2. AIMS To investigate the immunoexpression of cyclooxygenase 1 (COX-1), COX-2 and p53 in Crohns ileocolitis and to correlated this expression with clinical and histopathological parameters. METHODS Forty-five cases of Crohns disease, 16 cases of actinic colitis (diseased-control group) and 11 cases without a history of intestinal disease (normal control group) were studied. Hematoxylin-eosin-stained sections were submitted to histopathological analysis and the immunohistochemical expression of COX-1, COX-2 and p53 was evaluated by the streptavidin-biotin-peroxidase method. RESULTS Sixty percent of the Crohns disease patients were women and 40% were men, with 75.5% whites and 25.5% non-whites. The disease involved the terminal ileum in 44.5% of cases, ileum in 33.3%, colon in 20% and duodenum-ileum in 2.2%. A significant association was observed between COX-2 immunoreactivity and age < or =40 years. Histopathological analysis of Crohns disease samples showed mild or moderate crypt distortion (57.8% and 35.6% of cases), atrophy (6.6%), mild, moderate and marked chronic inflammation (46.7%, 26.7% and 20%), acute inflammatory activity (93.3%), ulceration (24.4%), mucin depletion (37.8%), Paneths cells (24.4%), intraepithelial lymphocytes (93.3%), and subepithelial collagen (6.7%). In the CD group, COX-1 immunoreactivity in epithelial and inflammatory cells was observed in 26.7% and 22.2% of cases, respectively. COX-2 immunoreactivity was detected in epithelial cells in 68.9% of cases and in inflammatory cells in 46.7%. A marginal difference in COX-2 reactivity was observed between epithelial and inflammatory cells in association with acute inflammatory activity and increase in intraepithelial lymphocytes. Comparison of the date among the threes groups (Crohns disease, actinic colitis and normal controls) showed a higher proportion of cases presenting COX-2 immunoreactivity in inflammatory cells in the Crohns disease group. No p53 reactivity was observed in all cases. CONCLUSIONS COX-2 immunoexpression is high in Crohns disease, which suggest a possible role of the protein in the pathogenesis of the inflammation. The absence of epithelial dysplasia in all Crohns disease samples was correlated with the lack of expression of p53.

The effects of pentoxifylline into the kidneys of rats in a model of unilateral hindlimb ischemia/reperfusion injury

PURPOSE To study the role of pentoxifylline (PTX) on remote kidney injury caused by muscle ischemia of left hindlimb of rats. METHODS After xylazine and ketamine anesthesia, the left hindlimb of rats (n=66) were submitted to 6 hours ischemia (clamping the left common iliac artery). Three groups were used: sham group (SG, n=6), early group (EG, n=30) with reperfusion after 4 hours and late group (LG, n=30) with reperfusion after 24 hours. The saline solution (EG1, n=10 and LG1, n=10) or PTX (40 mg.Kg-1) was administered in the reperfusion beginning (EG2, n=10/LG2, n=10) or divided in two doses in the ischemia beginning and reperfusion beginning (EG3, n=10/LG3, n=10). The plasmatic creatinokinase, urea, creatinine, sodium and potassium values were measure and histological samples from left kidney were prepared and H&E stained for scored cellular necrosis and degeneration of kidney tubules and thickness glomerulus determination. The apoptosis index was determined by immunohistochemical expression of the caspase-3. The tests of Mann-Whitney and Kruskal-Wallis (p <or= 0.05) were applied. RESULTS The urea (90.5 +/- 30.96 mg.dL-1), creatinine (2.28 +/- 0.54 mg.dL-1), potassium (16 +/- 3.66 mmol.dL-1) and mesangium thickness (0.97 +/- 0.42 microm) values were significantly higher in group LG3. There was no significantly difference of caspase 3 expression between EG2 (16.35 +/- 1.65%) and LG3 (15.57 +/- 2.54%), and both were significantly worse than SG (9.8 +/- 1.98%). CONCLUSIONS The PTX has some protecting effect on remote kidney injury due to hindlimb ischemia/reperfusion injury only in the early phase of reperfusion.

Expression of COX-2 in Stomach Carcinogenesis

BackgroundsGastric cancer is a frequent cause of cancer in Brazil. The understanding of gastric carcinogenesis is not completely known but the progress of the molecular biology has provided that the initiation and progression of gastric cancer process is a consequence of a cumulative series of multiple gene alterations.AimThe aim of the study is to investigate the relationship among cytoplasmatic COX-1 and COX-2, Bcl-2 and nuclear P53 in chronic gastritis, metaplasia, and intestinal and gastric cancer.Patients and MethodsCOX-1, COX-2, P53, and Bcl-2 were evaluated by immunohistochemistry in 34 gastric adenocarcinoma (GA) tissues obtained from gastric resection, 21 tissues of patients with chronic gastritis (CG), and 34 with intestinal metaplasia (IM) obtained from endoscopic biopsies.ResultsCOX-1 and COX-2 were expressed in more than 85% of the tissues. A correlation between COX-1 and COX-2 were observed (r = 0.66). P53 was positive in 29% CG, 20% of IM and in 59 % of GA. Bcl-2 was negative in all the CG, in 88% of IM, and in 85% of GA. P53 staining was expressed more frequently in gastric cancer when compared to CG (p = 0.05) or IM (p = 0.003). The expression of Bcl-2 was also higher in gastric cancer (p = 0.002) and in intestinal metaplasia (p = 0.04) when compared to CG. There were no difference between metaplasia and chronic gastritis for P53 or Bcl-2. The imunoreactivity of COX-2 in gastric cancer was higher in the intestinal type (58%) than in diffuse type. A higher expression of COX-2 was found in advanced gastric cancer (p = 0.019). P53 was also more frequent in node positive cancer (p = 0.04).ConclusionCOX-2 is probably involved in gastric carcinogenesis, being an early alteration in cancer. Although we observed in this study a correlation between COX-2 and depth of cancer, this association as a prognostic marker is not well defined. P53 and Bcl-2 was expressed mainly in gastric cancer, being probably a latest alteration in gastric development.