Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences

BACKGROUND: Coenzyme Q10 or ubiquinone is a redox component of the respiratory chain, which may be involved in the pathogenesis of cancer. METHODS: In order to better understand the role of this vitamin in the pathogenesis of breast cancer, a clinical trial including 200 women hospitalized for the biopsy and/or the ablation of a breast tumor was conducted. Ubiquinone plasma concentrations were determined simultaneously with vitamin E plasma concentrations (as antioxidant reference) by HPLC. RESULTS: A coenzyme Q10 deficiency was noted both in carcinomas (80 patients) and non-malignant lesions (120 patients), while vitamin E concentrations were within the normal range. A correlation was shown between the intensity of the deficiency and the bad prognosis of the breast disease based on high TNM and SBR values or the lack of estrogen receptors. However, neither cathepsin D level nor adenopathy invasion was related to ubiquinone levels. CONCLUSIONS: Since prooxidants may promote tumorigenesis, ubiquinone supplementation in breast cancer could be relevant.     

The prognosis of patients with gastric cancer possessing sex hormone receptors

Estrogen receptors (ER) and progesterone receptors (PgR) were immunohistologically investigated in 107 patients with gastric cancer who underwent curative resection. Both ER and PgR were detected only in the cancer cell nucleus. The ER positive rate was 27.7% for males and 31.0% for females, while the PgR positive rate was 9.2% for males and 11.9% for females. Clinicopathologically, the ER positive rate was slightly higher in young females and in cases of poorly differentiated gastric cancer. When cumulative survival rates were analyzed in relation to the presence or absence of receptors, the 10-year cumulative survival rate after surgery was significantly lower in the ER positive cases, being 15.7% cent, than in the ER negative cases, being 62.7%, and also significantly lower in the PgR positive cases, being 18.2%, than in the PgR negative cases, being 48.3%. The coexistence of ER and PgR in gastric cancer tissues suggests that the ER is physiologically active, or that ER positive gastric cancer is hormone-dependent. The poor prognosis of patients with receptor positive gastric cancer suggests that gastric cancer with these receptors is highly malignant.     

Does perioperative blood transfusion influence long-term prognosis of gastric cancer?

We analyzed the influence of packed red blood cell (PRBC) transfusions on the prognosis of 163 patients with gastric adenocarcinoma undergoing subtotal gastrectomy with a curative intention. Over a period of 15 years, our department admitted 505 patients with gastric adenocarcinoma, with curative subtotal gastrectomy being performed in 167 cases. Mean age was 62.2 years (range: 30-87); there was a predominance of males (104 cases; 63.8%). Excluding the four patients who died in the immediate postoperative period (first 30 days), the remaining 163 were reviewed twice yearly in our department until either they died or the study ended. Follow-up averaged 49.5 months, with a median of 36 months. Sixty-nine (42.3%) of the 163 patients received transfusions of PRBC. On correlating the variables with the transfusion, we found a statistical significance only between the rate of transfusion and patient age over 63 years (P < 0.01), with an evolution time of less than three months (P < 0.05) and in tumors of >4 cm (P < 0.05). The five-year survival rate of the nontransfusion patients was 56.9% and of the transfusion patients 40%, with statistically significant differences (P = 0.0132). On studying patients according to tumor stage, we found that blood transfusion had a statistically significant influence on prognosis only in patients with tumor stage III (P = 0.0051). In the univariate analysis of the remaining variables collected, the existence of abdominal tumor (P = 0.0307), tumor size (P = 0.00001), degree of involvement of the gastric wall (P = 0.00001), lymph node involvement (P = 0.00001) and tumor stage (P = 0.00001) revealed a statistically significant influence on prognosis. If we apply Cox's regression model to the variables that in the univariate analysis had a statistically significant influence on prognosis, we found that only tumor size and stage were independent predictors of survival. In our experience, PRBC transfusion does not influence the long-term survival of patients with resected gastric adenocarcinoma.     

Poor prognosis in early gastric cancer complicated by five or more positive nodes

BACKGROUND/AIMS: Despite the increased frequency of early gastric cancer, little is known about the clinicopathological features of early gastric cancers complicated by lymph node metastasis. This study was designed to determine whether the number of involved lymph nodes is associated with prognosis in patients with early gastric cancer. METHODOLOGY: Fifty one patients with node-positive early gastric cancer were reviewed retrospectively from hospital records. The patients were divided into two groups according to the number of positive nodes: a) 40 patients with 1-4 positive nodes, b) 11 patients with 5 or more positive nodes. RESULTS: The patients with 5 or more positive nodes showed poorer prognosis than patients with less than 5 positive nodes. CONCLUSIONS: Early gastric cancer patients with 5 or more positive nodes show a poorer prognosis than early gastric cancer patients with less than 5 positive nodes. Since surgery alone cannot completely cure patients with early gastric cancer complicated by 5 or more positive nodes, intensive postoperative chemo-immunotherapy should be administered to these patients.     

Plasma apolipoprotein profiles of male and female rats

To determine if sex differences exist in the apolipoprotein profile of the rat, the concentrations of the major apolipoproteins and lipids of 12-week-old male and female rats were measured in the plasma as well as in the individual lipoprotein fractions. Plasma apo B, triglyceride, and cholesterol concentrations were significantly higher in male rats than in female rats. Plasma concentrations of apo A-I, apo E, apo A-IV, and apo C-III did not differ between the sexes. Male rats had higher concentrations of apo B in the very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and the low density lipoproteins (LDL). These results further support the evidence that sex hormones influence lipoprotein metabolism in the rat.     

Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer

In myocardial SPECT perfusion imaging, reorientation algorithms from transaxial image planes are used to generate short- and long-axis views of myocardial tracer uptake. We performed phantom experiments with 201Tl to delineate how image reorientation affects the results of quantitative image analysis. METHODS: Thirty consecutive patient studies were analyzed to characterize the distribution of the angle of reorientation in a clinical setting. Short-axis SPECT images of a cardiac phantom with and without a 180 degrees cold-spot insert were reconstructed with three different backprojection filters (ramp, Metz and Butterworth) and reoriented through different angles ranging from 45 degrees to 89 degrees. Four interpolation algorithms were used to calculate from the transaxial images the pixel values of the reoriented images: (a) a simple interpolator that averages the pixel values of the eight neighboring pixels of the transaxial image; (b) a three-dimensional linear interpolator; (c) a hybrid interpolator that combines a two-dimensional linear in-plane with a one-dimensional cubic across-plane interpolation; and (d) a three-dimensional cubic convolution interpolator. Images were reoriented twice with opposite angles so that the original and the reoriented images could be directly compared. Circumferential profile analysis was applied to determine the root mean square error of corresponding profiles and the difference of the extent and the severity of perfusion defects. Single and multivariate analyses of variance (ANOVA) were used to compare the effects of the reorientation angle, the backprojection filter and the interpolation algorithm. RESULTS: In the clinical studies, the angle between the transaxial and reoriented images was 75 degrees +/- 10 degrees (s.d.). In 48 phantom experiments, multivariate ANOVA demonstrated that the backprojection filter and the interpolation algorithm significantly affect the circumferential profiles and the extent and severity of a perfusion defect (p < 0.05). In contrast, the angle of reorientation was not a significant factor (p = ns). By univariate analysis, the three-dimensional cubic interpolator was associated with significantly (p < 0.05) less error than the simple and three-dimensional linear algorithms. Relative computation times (simple interpolator = 100%) were 119% for the three-dimensional linear, 136% for the hybrid and 243% for the three-dimensional cubic interpolator. CONCLUSION: For quantitative analysis of myocardial SPECT perfusion images, a Metz filter for filtered backprojection in combination with a three-dimensional cubic convolution interpolation for image reorientation appears to offer improved accuracy.     

p53 protein expression in breast cancer as related to histopathological characteristics and prognosis

Reaction of Klebsiella aerogenes urease with diethylpyrocarbonate (DEP) led to a pseudo-first-order loss of enzyme activity by a reaction that exhibited saturation kinetics. The rate of urease inactivation by DEP decreased in the presence of active site ligands (urea, phosphate, and boric acid), consistent with the essential reactive residue being located proximal to the catalytic center. The pH dependence for the rate of inactivation indicated that the reactive residue possessed a pKa of 6.5, identical to that of a group that must be deprotonated for catalysis. Full activity was restored when the inactivated enzyme was treated with hydroxylamine, compatible with histidinyl or tyrosinyl reactivity. Spectrophotometric studies were consistent with DEP derivatization of 12 mol of histidine/mol of native enzyme. In the presence of active site ligands, however, approximately 4 mol of histidine/mol of protein were protected from reaction. Each protein molecule is known to possess two catalytic units; hence, we propose that urease possesses at least one essential histidine per catalytic unit.     

Parity and prognosis in breast cancer

Analysis of five-year disease-free survival rates in 608 women with operable breast cancer revealed that the reproductive history is a significant prognostic determinant. Overall parous women had a significantly higher cumulative five-year disease-free survival rate (60%), compared to the nulliparous (46%) (z = 2.5, p = 0.012). Significant differences were also noted when gravidity in addition to parity was taken as the determinant. The corresponding disease-free survival rates were 61% and 50%, respectively (z = 1.98, p = 0.048). Five-year survival rates were influenced in a similar manner by these variables but the observed differences were less significant. The trend toward higher survival rates in parous and gravidae women were noted in all tumor stages but achieved statistical significance only in stage III. The findings indicate that parity and gravidity affect not only the risk of breast cancer development but also the subsequent course of the disease. Parity seems to be a strong risk and prognostic factor than gravidity.     

Expression of p53 and vascular endothelial growth factor associated with tumor angiogenesis and prognosis in gastric cancer

We performed six immediate free flap reconstructions after tumor ablation in 5 children under the age of 15 years presenting with head and neck malignancy. One patient underwent free flap transfer on two separate occasions because of tumor recurrence. There were no flap losses nor were there any complications related to microvascular surgery. Although a pediatric head and neck malignant tumor is rare, surgical resection is the primary therapeutic role for those that are amenable to complete excision. Pediatric microsurgery provides a safe and reliable procedure for reconstruction of head and neck defects after extirpation of the tumor.     

Early gastric cancer mimicking advanced gastric cancer

The clinicopathological features of 37 early gastric cancers mimicking advanced gastric cancer were reviewed retrospectively, and were compared with 596 other early gastric cancers and 126 mp gastric cancers, defined as gastric cancer invading the muscularis propria of the stomach. A greater tumour size (P < 0.005), submucosal invasion (P < 0.005), lymph node and lymph vessel invasion (P < 0.005) and vascular invasion (P < 0.025) were found more frequently in early gastric cancers mimicking advanced gastric cancers than in other early gastric cancers. There were no significant differences in the clinicopathological findings between early gastric cancers mimicking advanced gastric cancers and mp gastric cancers. Patients with early gastric cancers mimicking advanced gastric cancers showed a lower survival rate than patients with other early gastric cancers, but a higher survival than those with mp gastric cancers. The macroscopic appearance of an advanced gastric cancer was an indicator of massive submucosal invasion and lymph node metastasis in early gastric cancer. As early gastric cancers mimicking advanced gastric cancers showed similar clinicopathological findings to mp gastric cancers, these cancers should be treated as mp gastric cancers.     

Ki-ras mutations and prognosis in colorectal cancer

A total of 191 colorectal adenocarcinomas, obtained from consecutive patients with a median follow-up of 6 years, were studied in order to evaluate the possible association of Ki-ras mutations with tumour stage, tumour differentiation and survival time. Resected full-cross tumour samples were screened for Ki-ras mutations in codons 12 and 13 using temporal temperature gradient gel electrophoresis (TTGE). Ki-ras mutations were detected in 62 (32%) of the samples. The most frequent mutation, observed in 21 samples, was from GGT to GAT changing glycine to aspartic acid in codon 12. The study did not show any association between Ki-ras mutations and Dukes' stage or tumour differentiation. Patients with Ki-ras mutations had a marginally shorter survival time (median 50 months) compared with patients without (median 59 months), but the difference was not statistically significant. The results indicate that Ki-ras gene mutations have no relevant prognostic importance in this cohort of colorectal cancer patients.     

Expression of p53 protein in colorectal cancer and its relationship to cell proliferative activity and prognosis

The expression of p53 protein in 66 cases of colorectal cancer and its relationship to cell proliferative activity, lymph node metastasis as well as prognosis were investigated by means of AB-PAP immunohistochemical technique. The results showed that 62.1% of colorectal cancer was positive. The cell proliferative activity and the frequency of lymph node metastasis in p53-positive cases were significantly higher than those of p53-negative cases (P < 0.05). The survival rate in patients with p53-positive tumors was significantly shorter than those with p53-negative tumors (P < 0.05). Our results suggest that the abnormal expression of p53 and cell proliferation associated with mutations are involved in both human carcinogenesis and lymph node metastasis of colorectal cancer. Examination of p53 expression is of value in understanding the degree of malignancy, and evaluating prognosis of the disease.     

p53 and prognosis in colorectal cancer

Treatment of rat liver arginase with N-bromosuccinimide results in modification of six tryptophan residues per enzyme molecule and is accompanied by loss of catalytic activity (E. Ber and G. Muzynska (1979) Acta Biochim. Pol. 26, 103-114). In order to probe the chemistry of N-bromosuccinimide inactivation and the role of tryptophan residues in catalysis, the two tryptophan residues of rat liver arginase, Trp122 and Trp164, have been separately mutated to phenylalanine using site-directed mutagenesis of the protein expressed in Escherichia coli. Both single Trp -> Phe mutant enzymes have kinetic parameters nearly identical to those for the wild-type enzyme. Treatment of native, wild-type, and each of the Trp -> Phe mutant enzymes with N-bromosuccinimide results in loss of absorbance at 280 nm and is accompanied by a loss of catalytic activity. However, treatment of the wild-type enzyme with N-bromosuccinimide in the presence of the arginase inhibitors NG-hydroxy-L-arginine or the combination of L-ornithine and borate protects against inactivation, even though tryptophan residues are modified. Treatment of the H101N and H126N mutant arginases with N-bromosuccinimide also results in loss of catalytic activity and modification of tryptophan residues. In contrast, the H141N mutant arginase is not inactivated by N-bromosuccinimide, indicating that His141 is the critical target for the N-bromosuccinimide inactivation of the enzyme.     

Plasma coagulation profiles in patients with severe primary pulmonary hypertension

Patients with primary pulmonary hypertension (PPH) benefit from treatment with anticoagulants, and histological findings suggest that in situ thrombosis of pulmonary vessels contributes to the pathogenesis of this disease. The mechanisms that cause a hypercoagulable state in the pulmonary vascular bed have not been fully investigated. This study compared plasminogen plasma activity, protein C and protein S plasma activities, fibrinogen and fibrin degradation products (FGDP and FBDP, respectively), von Willebrand factor antigen (vWF-Ag), prothrombin fragment F1.2, thrombin-antithrombin complexes (TAT), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) in 16 patients with PPH and in 16 healthy volunteers. In a subset of the PPH patients, these variables were also compared in simultaneously-obtained mixed-venous and arterial blood samples. Proteins C and S, FGDP, FBDP, and plasminogen levels as well as plasma concentrations of prothrombin fragment F1.2 and TAT were normal in the 16 patients with PPH. In contrast, the plasma activity of PAI was significantly elevated (p<0.0001). Arterial PAI levels were considerably higher than mixed venous PAI levels (p=0.0018), which may reflect intrapulmonary production. Furthermore, vWF-Ag levels were significantly elevated (p<0.0001), but there was no significant difference between mixed-venous and arterial blood. These data, on the whole, do not suggest increased thrombin activity in patients with primary pulmonary hypertension. However, the markedly elevated levels of plasminogen activator inhibitor as well as its transpulmonary gradient may provide a clue to locally impaired fibrinolysis in the pulmonary vascular bed.     

胃癌组织中HER2基因状态与p21蛋白表达的关系研究

Objective:We aimed to analysis the HER2 gene status and its relationship with p21 protein expression in gastric carcinoma.Methods:Fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) techniques were used to detect HER2 gene status and p53 protein in 59 cases of gastric cancer.Results:FISH detection of HER2 gene amplification rate was 16.9% (10/59),HER2 gene amplification in 49 cases without copy number gain and gene amplification were a total of 49.2% (29/59).HER2 protein expression was 42.4% (25/59),HER2 gene amplification rates in patients with +++,++ HER2 protein expression were 3/3 and 5/8,while in patients with + HER2 protein expression,it was 2/14,there was significant difference (P < 0.05).p21 protein expression rate was 49.2% (29/59),HER2 gene amplification rates and p21 protein expression had significant difference in tumor invasion depth,lymph node metastasis (P < 0.05);had no statistical significance in histological type,age,gender differences (P > 0.05).Conclusion:HER2 gene amplification rate and gene copy number had positively correlation with p21 protein expression,HER2 gene status and expression of p21 protein combined detection can provide a reference value in gastric cancer metastasis,patient's condition development and prognosis,it also can guide clinical development of individual treatment.     

Sialosyl Tn antigen expression is associated with the prognosis of patients with advanced gastric cancer

BACKGROUND: Several studies have revealed a correlation between sialosyl Tn antigen (STN) and certain clinicopathologic features of various cancers, and that STN is an independent prognostic factor. However, the clinical significance of the expression of STN in gastric cancer has not been reported. Thus, the purpose of this study was to evaluate immunohistochemically the clinical significance of expression of STN in gastric cancer. METHODS: The expression of STN in surgically resected specimens of human gastric cancer was evaluated immunohistochemically using a monoclonal antibody (TKH-2), in 60 patients whose serum STN levels were measured and in 54 patients with advanced cancer who had been followed for more than 5 years after gastrectomy. The correlations between the level of STN expression and clinicopathologic factors were analyzed. The staining intensity was graded as follows: (-), less than 5% of the cancer cells expressed STN; (+), 5-50%; (++), more than 50%. RESULTS: Sialosyl TN antigen staining was detected mainly on the cell membrane, in the cytoplasm, and in the luminal contents, and 57.2% of the 60 specimens expressed STN, whereas the corresponding value for positive serum levels was 15%. A higher percentage of advanced tumors expressed STN than did the early cases, but the difference was not statistically significant. All cases with strong staining, the (++) cases, were advanced cases either with lymph node metastases or with cancer invading in or beyond the muscle layer proper. The expression of STN appeared to be related to the clinical stage, the extent of cancer invasion, and the presence of lymph node metastases. Sialosyl TN antigen was detected in the serum in less than 6% of the patients whose tumors were (-) or (+) for STN expression, and in 86.7% of the patients whose tumors expressed high levels of STN (++). The estimated 5-year survival in advanced cases (Stage III) was significantly better in those with negative STN expression than in those with positive STN expression (P < 0.01). CONCLUSIONS: These results suggest that STN may be a useful marker associated with the prognosis of patients with advanced gastric cancer.     

Parotid saliva protein profiles in caries-free and caries-active adults

The recent emergence and spread of dengue hemorrhagic fever in the Americas have been a major source of concern. Efforts to control this disease are dependent on understanding the pathogenicity of dengue viruses and their transmission dynamics. Pathogenicity studies have been hampered by the lack of in vitro or in vivo models of severe dengue disease. Alternatively, molecular epidemiologic studies which associate certain dengue virus genetic types with severe dengue outbreaks may point to strains with increased pathogenicity. The comparison of nucleotide sequences (240 bp) from the E/NS1 gene region of the dengue virus genome has been shown to reflect evolutionary relationships and geographic origins of dengue virus strains. This approach was used to demonstrate an association between the introduction of two distinct genotypes of dengue type 2 virus and the appearance of dengue hemorrhagic fever in the Americas. Phylogenetic analyses suggest that these genotypes originated in Southeast Asia and that they displaced the native, American genotype in at least four countries. Vaccination and other control efforts should therefore be directed at decreasing the transmission of these "virulent" genotypes.     

Ki-67 immunostaining and prognosis in laryngeal cancer

A 7-year-old male Husky dog developed atrophy of the right masseter muscle and pruritus of the right side of the face. A myogenic origin was excluded using muscular biopsy. Electrophysiologically, there was involvement of the motor and sensory fibers of the trigeminal nerve, suggesting a lesion located between the brainstem and the trigeminal ganglion. On MRI examination, a nodular mass was detected in the right caudal fossa. This mass was characterized by intense enhancement after injection of contrast medium. Because of the progressive clinical signs, electrophysiology, and MRI results, a presumptive diagnosis of a trigeminal nerve schwannoma was made. The animal's condition improved slightly with corticosteroids. The dog underwent euthanasia 3 months after initial presentation. Necropsy was not performed.