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[A study on the relationship between the production of cytokines and the biological features of cachexia using renal cell carcinoma heterotransplanted to nude mice].

We studied the biological features of cacheixa using renal cell carcinoma heterotransplanted to nude mice (JRC 11) where cachexia was caused after the inoculation of tumour. The results of our study were as follows; 1) The JRC 11 tumour expressed mRNA of interleukin-6 by the analysis using the polymerase chain reaction method (PCR). 2) The human IL-6 was detected in the sera of nude mice according to the growth of JRC 11. On the other hand, human IL-1-beta, human tumour necrosis factor (hTNF)-alpha and human interferon (hIFN)-gamma were not detected. 3) The serial body weight of nude mice excluding tumour weight decreased at the 3rd week after the inoculation of tumour compared with tumour non-inoculated mice (control). Furthermore, the experimental group performed the resection of JRC 11 at the 3rd week after the inoculation of tumour showed a re-increase in the body weight, and reached the same weight as that of the control group at the 6th week after the inoculation of tumour. At the same time, serum hIL-6 was not detected in this group. 4) The serial weight of visceral organs including the liver, kidney and spleen began to decrease at the 3rd week after the inoculation of tumour compared with the control group. We conclude that serum IL-6 is defined as a promoter of cachexia in renal cell carcinoma relating to paraneoplastic syndrome.

Animals↗

Comparative biological features of a rat liver abscess model induced with three Fusobacterium necrophorum strains.

Several biological features were compared in a rat liver abscess model, using intraportal inoculations with 3 bovine strains of Fusobacterium necrophorum which varied in virulence. Serum alanine aminotransferase activities were increased significantly (P less than 0.05) in rats inoculated with F necrophorum 2101 by postinoculation hours 6, 12, and 24. Thereafter, alanine aminotransferase values returned to base line for the remainder of the experiment. Also, rats inoculated with F necrophorum 2101 had a significantly greater (P less than 0.05) weight loss than did the control rats during the first 5 postinoculation days and developed leukocytosis characterized by a neutrophilia with a left shift. The duration of the bacteremia was related directly to the virulence of the F necrophorum strain. Fusobacterium necrophorum 2101, a biotype A which was the most virulent, induced the most persistent bacteremia; F necrophorum 2035, a biotype B which was the least virulent, produced the shortest bacteremia; and F necrophorum 2030, a biotype AB which was of intermediate virulence, led to bacteremia of intermediate duration. Plasma endotoxin was demonstrated intermittently during the first 24 hours, but did not correlate with the bacteremia.

Alanine Transaminase↗

Changes of biological features in breast cancer cells determined by primary chemotherapy.

BACKGROUND: To evaluate the changes in the biological features of breast cancer cells induced by primary chemotherapy (PCT) and their possible relationship with the response to therapy we performed an extensive immunohistochemical study before and after PCT. PATIENTS AND METHODS: PCT was administered to 29 women with breast cancer. On specimens obtained by tru-cut and post-chemotherapy surgery we analyzed the following parameters: histology, histologic grade, apoptotic index, hormone receptor levels, Ki67, PCNA, EGFr, bcl-2, p53, p170. The significance of the changes induced by PCT and their correlations with the type of response were evaluated. RESULTS: Twelve patients achieved a partial response with PCT. No baseline biological parameter correlated with the type of response. After PCT we observed a significant increase in the apoptotic index (p = 0.000), PCNA (p = 0.036), EGFr (p = 0.005), and p170 expression (p = 0.001), regardless of the type of chemotherapy administered (anthracyclines, 25 cases, or CMF, 4 cases). Responder patients displayed a significant decrease in ER levels (p = 0.015), whereas in non responders there was an increase in PCNA (p = 0.008) and EGFr expression (p = 0.002). The apoptotic index and p170 expression rose after PCT regardless of the type of response. CONCLUSIONS: PCT induced significant variations in the phenotype of breast cancer cells. These changes might reflect the selection of new neoplastic clones with different biological properties and so could facilitate the choice of appropriate chemotherapy agents.

Adult↗

Clinical and cell biological features related to cellular drug resistance of childhood acute lymphoblastic leukemia cells.

Several clinical and cell biological features, such as sex, age, leukemic cell burden, morphologic FAB type, and immunophenotype, have prognostic value in childhood acute lymphoblastic leukemia (ALL). The explanation for their prognostic significance is unclear, but might be related to cellular drug resistance. We prospectively studied the relation between the above mentioned features with resistance to 13 drugs in 144 childhood ALL samples obtained at initial diagnosis. The MTT assay was used for drug resistance testing. The interindividual differences in drug resistance were very large and exceeded those between the several subgroups. There was generally no significant relation between sex, leukemic cell burden, and FAB type with drug resistance. However, subgroups with a worse prognosis as defined by age (< 18 months and > 120 months at diagnosis) or immunophenotype (pro-B ALL and T-ALL) did show relatively resistant drug resistance profiles as compared to the subgroups with a better prognosis (age 18-120 months, common and pre-B ALL). Within the group of common and pre-B ALL and compared to the intermediate age-group, samples of the younger children were significantly more resistant to daunorubicin, mitoxantrone and teniposide, and samples of the older children were significantly more resistant to prednisolone and mercaptopurine. Pro-B ALL samples were significantly more resistant to 1-asparaginase and thioguanine, and T-ALL samples were significantly more resistant to prednisolone, dexamethasone, 1-asparaginase, vincristine, vindesine, daunorubicin, doxorubicin, teniposide, and ifosfamide, than the group of common and pre-B ALL cases. We conclude that the prognostic significance of age and immunophenotype in particular may be explained, at least partly, by its relation with resistance to certain drugs. The results of this study may be useful for future rational improvements of chemotherapeutic regimens in childhood ALL.

Antineoplastic Agents↗

Comparison of clinical and biologic features between myeloid and lymphoid transformation of Philadelphia chromosome positive chronic myeloid leukemia.

Analysis of clinical and biologic features of chronic myeloid leukemia (CML) in blast crisis (BC) was performed on 36 patients: 25 had myeloid and 11 had lymphoid transformation. The median duration from diagnosis to onset of BC was significantly shorter in patients with lymphoid BC (6 months) than in those with myeloid BC (41 months). Patients in lymphoid transformation showed better response to therapy and had a significantly longer median survival time after BC than patients with myeloid transformation (56% vs 0% and 10 months vs 4 months, respectively). The leukemic cells from all the patients with lymphoid BC showed B-cell immunophenotype, confirmed by the presence of immunoglobulin (Ig) heavy chain gene rearrangements in the five patients studied. Two of the eight patients with complete marker study expressed myeloid-associated antigens on the blasts. A high incidence of CD7 expression (7/17 or 41%) was found in patients with myeloid BC, but none of the patients who had DNA analysis showed rearrangement of T-cell receptor beta chain gene. Chromosomal abnormalities +8, +19, +21, and i(17q) were detected only in the patients with myeloid BC but not in those with lymphoid BC. Combined analysis of the patients in this series and those reported previously has revealed a statistically significant difference in the distribution of bcr breakpoints between myeloid and lymphoid BC: the bcr breakpoints in more than half of the patients with myeloid crisis were mapped to Zone 2 while those in patients with lymphoid crisis occurred most frequently in Zone 3.

Adolescent↗

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones.

OBJECTIVES: To investigate differences in the biological features of prostate cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.

Aged↗

Characterization of acute myeloid leukemia (AML) coexpressing lymphoid markers: different biologic features between T-cell antigen positive and B-cell antigen positive AML.

The clinical and biologic characteristics of acute myeloid leukemia (AML) with coexpression of lymphoid-associated antigens (Lym+ AML) were studied from 39 cases who represented 24% of 161 newly diagnosed de novo AML. Twenty-seven cases (16.8%) were positive for the expression of T-cell markers (T+ AML) and 12 (7.5%) for B-cell markers (B+ AML). Chromosomal abnormalities t(9;22)(q34;q11) and t/del(11)(q23), which were considered to be associated with acute leukemia coexpressing markers of more than one cell lineage, were detected in five and in four patients, respectively. There was no prognostic significance of B-cell or T-cell antigen expression in AML. Of 12 T+ AML cases in which cells were available for gene analysis, all showed germline configuration of immunoglobulin heavy chain and T-cell receptor beta chain genes, while seven of nine B+ AML showed rearrangements of either or both of the genes. Double labeling of the cells with myeloperoxidase and lymphoid markers demonstrated that individual blasts in all the five T+ AML tested were simultaneously expressing myeloperoxidase activity and CD7; however, most blasts in the three B+ AML studied expressed either myeloperoxidase activity or CD10, but not both. In eight of the nine T+ AML tested, the T-cell antigen-positive leukemic blasts were significantly decreased to less than 10%, after in vitro culture with the differentiation-inducing agent phorbol ester. B-cell markers remained positive (> or = 20%) on the cells in the two B+ AML who had the same study. These findings suggested that T+ AML and B+ AML might have different biologic features. Further studies on more patients are needed to clarify this point.

Acute Disease↗

Biological features and preoperative evaluation of mediastinal nodal status in non-small cell lung cancer.

BACKGROUND: To examine whether biological features of primary tumor can help preoperative evaluation of mediastinal nodal status in non-small cell lung cancer. METHODS: A total of 450 patients who underwent tumor resection and mediastinal dissection were reviewed. p53 status and proliferative fraction (PI) were evaluated immunohistochemically. RESULTS: The accuracy of preoperative evaluation of mediastinal nodal status with computed tomography (CT) was 72.2%; mediastinal nodal metastases had not been revealed until operation in 59 patients (13.1%) (false-negative), and no metastasis was revealed in 66 patients (14.7%) although mediastinal nodal enlargement had been demonstrated by CT (false-positive). The number of false-negative patients was significantly larger when p53 aberrant expression was positive or when PI was higher. Combined with p53 status and PI, there were 27 false-negatives (24.1%) among patients with aberrant p53 expression and higher PI, whereas only two false-negatives (1.5%) among those with negative p53 expression and lower PI. CONCLUSIONS: Mediastinoscopy may be recommended for tumor showing aberrant p53 expression and higher PI, even when CT demonstrates no mediastinal nodal enlargement.

Aged↗

Differences in biological features of gastric dysplasia, indefinite dysplasia, reactive hyperplasia and discriminant analysis of these lesions.

AIM: To investigate the differences in biological features of gastric dysplasia (Dys), indefinite dysplasia (IDys) and reactive hyperplasia (RH) by studying the biomarker alterations in cell proliferation, cell differentiation, cell cycle control and the expression of house-keeping genes, and further to search for markers which could be used in guiding the pathological diagnosis of three lesions. METHODS: Expressions of MUC5AC, MUC6, adenomatous polyposis coli (APC), p53, Ki-67, proliferation cell nuclear antigen (PCNA) and EGFR were studied by immunohistochemistry with a standard Envision technique in formalin-fixed and paraffin-embedded specimens from 43 RH, 35 IDys, 35 Dys and 36 intestinal type gastric carcinomas (IGC). In addition, Bayes discriminant analysis was used to investigate the value of markers studied in differential diagnosis of RH, IDys, Dys and IGC. RESULTS: The MUC5AC and MUC6 antigen expressions in RH, IDys, Dys and IGC decreased gradually (MUC5AC: 86.04%, 77.14%, 28.57%, 6.67%; MUC6: 65.15%, 54.29%, 20.00%, 25.00%, respectively). The expressions of the two markers had no significant difference between RH and IDys, but were all significantly higher than those of the other two lesions (MUC5AC: chi2=27.607, 38.027 and 17.33, 26.092; MUC6: chi2=16.54, 12.665 and 9.282, 6.737, P<0.01). There was no significant difference between RH and IDys, Dys and IGC in MUC6 expression. The APC gene expression in the four lesions had a similar decreasing tendency (RH 69.76%, IDys 68.57%, Dys 39.39%, IGC 22.86%), and it was significantly higher in the first two lesions than in the last two (chi2=7.011, 16.995 and 14.737, 19.817, P<0.05). The p53 expression in RH, IDys, Dys and IGC was 6.98%, 20%, 57.14% and 50%, respectively. There was no significant difference between RH and IDys or Dys and IGC, but the p53 expression in RH and IDys was significantly lower than that in Dys and IGC (chi2=7.011, 16.995 and 14.737, 19.817, P<0.01). The Ki-67 label index was significantly different among four lesions (RH: 0.298+/-8.92%, IDys: 0.358+/-9.25%, Dys: 0.498+/-9.03%, IGC: 0.620+/-10.8%, P<0.001). Positive immunostaining of PCNA was though observed in all specimens, significant differences were detected among four lesions (F=95.318, P<0.01). In addition, we used Bayes discriminant analysis to investigate molecular pathological classification of the lesions, and obtained the best result with the combination of MUC5AC, Ki-67 and PCNA. The overall rate of correct classification was 67.4% (RH), 68.6% (IDys), 70.6% (Dys) and 84.8% (IGC), respectively. CONCLUSION: Dys has neoplastic biological characteristics, while RH and IDys display hyperplastic characteristics. MUC5AC and proliferation-related biomarkers (Ki-67, PCNA) are more specific in distinguishing Dys from RH and IDys.

Biomarkers↗

Biological features and in vitro chemosensitivity of a new model of human melanoma.

The M14 human melanoma cell line was characterized either for some biological features in vitro and in vivo or for responsiveness to a panel of anti-tumor agents of clinical interest. The results of our study show that the M14 cells in culture resemble the in vivo melanomas both biologically and functionally, thus suggesting the usefulness of employing this line as a preclinical model for cancer treatment studies.

Animals↗

[The relationship of cellular DNA content with clinical stage and biological features of colorectal cancer].

The purpose of this study was to explore the relationship of cellular DNA content with clinical stage and biological features of cancer. Flow cytometry was performed on fresh specimens from 86 patients from 1997 to 1998. Forty-five (53.3%) specimens were found to contain cells with abnormal DNA (DNA nondiploidy). Although none of the sex, age, site, differentiation variables correlated with flow cytometric DNA ploidy, nondiploidy was associated with Dukes' stage and lymph node metastasis. Duke's A stage tumors were more frequently diploid than were more advanced tumors, but no difference between Duke's B, C and D stages were observed. These findings suggest that ploidy is associated with some pathological factors.

Aged↗

Intestinal microsporidiosis in human immunodeficiency virus-infected patients with chronic unexplained diarrhea: prevalence and clinical and biologic features.

Eighteen patients infected with human immunodeficiency virus and with chronic unexplained diarrhea were prospectively studied to investigate the prevalence and clinical and biologic features of intestinal microsporidiosis. All patients underwent extensive evaluation for bacterial, viral, and parasitic pathogens. Enterocytozoon bieneusi was found in 9 patients (50%; 95% confidence interval, 27-73) in stools and duodenal and jejunal biopsies. In 8 patients, it was the sole pathogen found. Other pathogens were also isolated from the intestinal tracts of 4 patients, but diarrhea remained unexplained in 6. Patients with intestinal microsporidiosis had significantly lower mean Karnofsky scores (69.4 vs. 85.5, P = .009), CD4 cell counts (18.6 vs. 209.8/microL, P = .02), and D-xylose absorption tests (0.13 vs. 0.36 g/L, P < .001) than did patients without intestinal microsporidiosis. Intestinal microsporidiosis appears to be a frequent cause of unexplained chronic diarrhea in patients with AIDS and is associated with diminished D-xylose absorption.

AIDS-Related Opportunistic Infections↗

Extremely short stature: influence of each parent's height on clinical-biological features.

UNLABELLED: Idiopathic extremely short stature probably has several causes. OBJECTIVE: To evaluate the influence of each parent's height on clinical-biological features. METHODS: 57 patients without intrauterine growth retardation seen at 7.9 +/- 0.4 years for height < or = -3 SD were classified according to the difference between their target height and actual height: < 2 SD in familial short stature (FSS, n = 28) and >2 SD in non-FSS (n = 29). RESULTS: Height decreased from -0.5 +/- 0.1 SD at birth to -2 +/- 0.2 SD at 1 year and -2.7 +/- 0.1 SD at 3 years, but the changes in the two groups were similar. FSS children were shorter than non-FSS children both at birth (p = 0.03) and as adults after growth hormone (GH) treatment (p < 0.05), but their plasma insulin-like growth factor I concentrations and GH peaks were similar. The FSS children fathers' heights were more frequently below -2 SD (64%) than the mothers' heights (35%) and were correlated with height at first evaluation (p < 0.05). For the whole population, the mothers' heights were correlated with birth weight (p < 0.05) and with height at first evaluation (p < 0.03). CONCLUSION: This study confirms the influence of the mother's height on birth weight and shows how of the father's height influences idiopathic extremely short stature.

Adolescent↗

[Effect of lipopolysacharide on the biological features and growth factor secretion power of U937 cell line].

OBJECTIVE: To investigate the effect of lipopolysacharide (LPS) in different concentrations on the biological features and growth factor secretion power of U937 cell line. METHODS: In vitro cultured U937 cells were stimulated by 0 (as control), 0.1, 1.0, 10.0, 50.0 and 100 micro g/ml LPS respectively for 24 hours. Thereafter, the cell proliferation ability was determined by MTT method. The cell apoptosis rate was determined by flow cytometry. The changes in the contents of transforming growth factor beta(1) (TGFbeta(1)) and vascular endothelial growth factor (VEGF) of the supernatant of the cell culture were assessed by ELISA. RESULTS: Apoptosis and TGFbeta(1) secretion could be induced by LPS in dose of 0.1 to 100 micro g/ml when compared with that without LPS challenge (P < 0.05 - 0.01). In detail, LPS in lower dose (0.1, 1.0 and 10.0 micro g/ml) could promote the proliferation of U937 (P < 0.05 - 0.01) but exerted no effect on VEGF secretion. In contrary, LPS in high dose (50 and 100 micro g/ml) could promote VEGF secretion (P < 0.01) but exerted no effects on the proliferation of U937 cells. CONCLUSION: U937 cells could be activated to increase the secretion of TGFbeta(1) by LPS in optimal dose of 0.1 - 10.0 micro g/ml, but the secretion of VEGF could only be promoted by LPS in higher concentration.

Apoptosis↗

Early-onset hereditary prostate cancer is not associated with specific clinical and biological features.

BACKGROUND: Familial prostate cancer (CaP) accounts for 15-20% of all CaP, and hereditary CaP for 5-10% of patients. Few data are available concerning their clinical and biological features. METHODS: We compared diagnostic modalities, age, clinical stage, PSA, and tumor grade at diagnosis in CaP patients according to familial CaP profile: hereditary (HR) (> or =3 CaP), familial nonhereditary (FNH) (= 2 CaP), and sporadic CaP. Only cases diagnosed after January 1, 1987 (PSA-available period) were included. We considered as informative sporadic (IS) cases those probands with 2+ nonaffected brothers at least 50 years old. Finally, 267 CaP (230 probands and 37 affected brothers) were studied. RESULTS: In multivariate analysis, the only specific parameter significantly associated with HR and FNH CaP was early age at diagnosis; mean ages were 65.3 years (HR), 67 years (FNH), and 70.9 years (IS) (P < 0. 0001). No significant difference was observed concerning clinical stage, PSA, and tumor grade. In addition, diagnostic modalities were similar in the three groups. CONCLUSIONS: Our data confirm the occurrence of early-onset CaP in hereditary families. Although the clinical and biological presentation of HR CaP remains controversial, the lack of specific features observed in our study leads us to conclude that there is no difference in the aggressiveness of the disease in hereditary compared to sporadic CaP.

Aged↗

Clinical and biologic features in the prognosis and treatment of neuroblastoma.

Recent advances in the management of neuroblastoma have their basis in an increasing understanding of the biologic diversity that typifies these tumors. Current therapy is defined by risk of disease progression or relapse and has become best delineated in lower-stage disease and in infants. Older children with disseminated disease continue to exhibit very poor overall outlook, despite recent advances in dose-intensive chemotherapy. This review updates the clinical and biologic features of neuroblastoma that have a significant impact on prognosis and therapeutic design and discusses recent trends and controversies in the treatment of specific subsets of patients.

Humans↗

Prion proteins from susceptible and resistant sheep exhibit some distinct cell biological features.

It is well established that natural polymorphisms in the coding sequence of the PrP protein can control the expression of prion disease. Studies with a cell model of sheep prion infection have shown that ovine PrP allele associated with resistance to sheep scrapie may confer resistance by impairing the multiplication of the infectious agent. To further explore the biochemical and cellular mechanisms underlying the genetic control of scrapie susceptibility, we established permissive cells expressing two different PrP variants. In this study, we show that PrP variants with opposite effects on prion multiplication exhibit distinct cell biological features. These findings indicate that cell biological properties of ovine PrP can vary with natural polymorphisms and raise the possibility that differential interactions of PrP variants with the cellular machinery may contribute to permissiveness or resistance to prion multiplication.

Amino Acid Sequence↗