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Biomedical subjects

J C Araya

Publications and source records attributed to J C Araya.

At least 37 records · Page 2Linked to original sources

[Hepatocellular carcinoma. General aspects of diagnosis and treatment].

Hepatocellular carcinoma is the most frequent form of primary hepatic cancer and has a high dissemination capacity. About 90% of tumors develop over a pre-existing cirrhosis but they also may occur in a normal liver. It has a higher frequency among males and 80% of tumors have clinical manifestations. It is associated to hepatitis B and C virus infection, alcoholism, cirrhosis of any etiology, consumption of aflatoxin Bl, oriental race and familial history. Patients are staged using classifications proposed by Okuda, Child-Pugh and the performance status test. Alpha feto protein is useful for diagnosis and follow up Abdominal ultrasound, hepatic scintiscan, angiography with lipiodol, CAT scan and nuclear magnetic resonance have a high diagnostic yield. Non surgical therapeutic alternatives include intratumoral alcoholization, chemoembolization and other such as tamoxifen and monoclonal antibodies. Surgical treatment is based on hepatic resection, whose magnitude depends on hepatic function. Hepatic transplantation is a new therapeutic alternative for patients in whom resection is not feasible and have a single small tumor without metastases.

Biomarkers, Tumor↗

Effects of anti-erbB-2 (HER-2/neu) recombinant oncotoxin AR209 on human non-small cell lung carcinoma grown orthotopically in athymic nude mice.

The recombinant oncotoxin AR209 [e23(Fv)PE38KDEL; formerly OLX-209] was developed to treat neoplasia that expresses the c-erbB-2 (HER-2/neu) protein product p185(erbB-2). The AR209 compound contains a single-chain antibody domain specific for p185(erbB-2), coupled with a portion of the Pseudomonas exotoxin. The drug has been shown to be effective in inhibiting cells that overexpress erbB-2 due to gene amplification and in cells that do not contain amplified erbB-2 but express slightly higher levels of the protein than normal cells do. To test the efficacy of AR209 on human lung tumors, athymic nude mice were inoculated intrathoracically with a cell line derived from a poorly differentiated lung adenocarcinoma. This cell line, termed 201T, expresses moderately elevated levels of p185(erbB-2) 7.6-fold over normal bronchial epithelium. Mice treated with i.v. injections of AR209 for 5 weeks after orthotopic tumor implantation had smaller tumors and in 20% of cases showed no evidence of disease. The data from this study indicate that AR209 may be an effective treatment for patients with non-small cell lung cancers that express p185(erbB-2).

Animals↗

[Gallbladder cancer. Case-control study].

Gallbladder cancer is the principal oncological cause of death in chilean women and cholelithiasis is a well recognized risk factor. Aiming to unravel other risk factors for gallbladder cancer, we compared 50 patients subjected to cholecystectomy in whom a gallbladder cancer was found with 50 age and sex matched operated controls without cancer. Subjects were clinically assessed and interrogated about demographic, obstetrical features and feeding features. Multiples and early pregnancies were factors significantly associated to the development of gallbladder cancer. Twenty subjects (44%) with cancer knew that they had cholelithiasis and 41 patients in each group were symptomatic. It is concluded that pregnancy may be a risk factor for gallbladder cancer probably due to the lithogenic effect of its hormonal changes. Also, early cholecystectomy in symptomatic individuals may be an effective preventive measure.

Adult↗

[Proliferating cell nuclear antigen in cervical cancer and precursor lesions].

The aim of this study was to study the degree of cellular proliferation quantifying the immunohistochemical expression of the proliferating cell nuclear antigen. We assessed paraffin embedded samples of 25 infiltrating epidermoid cervical carcinomas, 76 precursor lesions (34 of low and 42 of high grade), 29 normal and 13 metaplastic epidermoid epithelia. Mean values of proliferating cell nuclear antigen expression were 13.7% in normal epithelia, 15.7% in epidermoid metaplasia, 37.1% in low grade precursor lesions (35.3% in condilomas and 38.8% in mild dysplasia), 48.7% in high grade lesions (47.9% in moderate dysplasias, 50.5% in severe dysplasias and 50% in carcinoma in situ) and 54.7% in infiltrating carcinoma. There were differences in proliferating cell nuclear antigen expression nd mitotic index between low grade precursor lesions and high grade lesions and infiltrating carcinoma. No correlation was observed between mitotic index and proliferating cell nuclear antigen expression. We conclude that infiltrating epidermoid cervical carcinoma and its precursor lesions have a high level of proliferative activity, demonstrated by a high percentage of cells in active phases of the cellular cycle.

Carcinoma, Squamous Cell↗

[Gallbladder cancer: immunohistochemical expression of the protein related to estrogen receptor (p29) and of the protein induced by estrogen (pS2)].

The high frequency of gallbladder cancer in women suggests a role for estrogens in its development. The aim of this study was to study the immunohistochemical expression of p29 estrogen receptor associated protein and pS2 estrogen induced protein in 111 pathological samples of gallbladder carcinoma, coming from 88 women and 23 men, 30 metastases of gallbladder cancer, coming from 25 women and 5 men and in 25 non-tumoral gallbladders. In the latter, p29 protein was positive in 12 samples (48%) and pS2 in 15 cases (60%). p29 was positive in 40% and pS2 in 32% of tumors. p29 expressed with higher frequency in metastases than in primary tumors (57 and 31% respectively, p < 0.02). Early tumors had a significantly lower expression of p29 than advanced tumors or than metastases. Both proteins expressed in 18% of samples (synchronic expression) whereas one of both proteins did so in 60% of cases (asynchronic expression). We conclude that most gallbladder cancer samples express proteins associated to estrogen receptor or induced by estrogens.

Adenocarcinoma↗

[Laparoscopic cholecystectomy makes difficult the analysis of gallbladder mucosa. Morphometric study].

Laparoscopic gallbladder surgery damages gallbladder mucosa, impeding an adequate histological examination. We studied gallbladder samples coming from 56 conventional and 44 laparoscopic cholecystectomies performed in patients with chronic cholecystitis without signs of acute inflammation. The length of each examined sample and the length of the portion where superficial epithelia was not found was measured. No differences in sample length was found between both types of cholecystectomy. However; the segment with superficial mucosa was significantly shorter in the samples coming from laparoscopic surgery. Seventeen samples did not contain mucosa at all and 14 of these (82%) came from laparoscopic procedures. Eighty six percent of samples coming from laparoscopic surgery were considered inadequate for histological study compared to 36% of samples coming from conventional cholecystectomy. It is concluded that laparoscopic cholecystectomy hampers the study of gallbladder mucosa and may have an impact on the diagnosis of neoplastic gallbladder lesions.

Cholecystectomy↗

[Proliferating cell nuclear antigen (PCNA) in patients with malabsorption syndrome: comparative study with morphometric parameters].

The study of small bowel mucosa is routine in the study of patients with malabsorption. We report 16 children aged from 8 months to 6 years old (2 with giardiasis, 8 with primary malnutrition and 5 with celiac disease) in whom a morphometric and PCNA immunostaining was performed in the small intestinal biopsy. Positivity for PCNA was found in the lower portion of the crypts reaching 156 microns of heigh in patients with giardiasis, 103 microns in primary malnutrition and 182 microns in celiac disease (p < 0.01 compared to primary malnutrition). A negative and significant correlation was found between the degree of architectural disorder (expressed the mucosal index) and the proliferative portion of the crypts (expressed as the percentage of PCNA(+) crypts. We propose these methods as complements to the small bowel mucosa histopathological study in the diagnosis of celiac disease, to assess the degree of architectural disorder and the proliferative activity.

Child↗

[Expression of p29, estrogen receptor related protein in primary breast carcinoma. Methodological, anatomoclinical, and DNA content analysis].

The aim of this work was to assess the immunohistochemical detection of a estrogen receptor related protein (p29) in 48 histological samples of primary mammary carcinoma and its relationship to clinical, morphological and ADN content parameters. p29 protein was positive in 62.5% of samples. Over 50% of samples had a moderate or intense immunohistochemical staining (staining index over 16) and 77% has a heterogeneous expression of p29 protein. Seventy six percent of p29 positive and 53% of p29 negative tumors had a proliferation fraction over 10% (determined by the S fraction with flux cytometry). No relationship between p29 expression and the analyzed anatomoclinical variables was found. These results highlight this immunohistochemical method as an alternative to more complex and difficult biochemical techniques. On the other hand, the good results obtained in formalin fixed tissues allow retrospective studies in mammary carcinoma samples.

Biomarkers, Tumor↗

[Gallbladder cancer in the IX Region of Chile. Impact of the anatomopathological study of 474 cases].

We studied prospectively 474 cases (83% female with a female:male ratio of 5:1) of gallbladder carcinoma diagnosed in a period of 7 years. Twenty two percent of patients were younger than 50 years old. Ninety percent of tumors were adenocarcinomas. In 1987, 45% of cases were diagnosed in metastases compared to 1993, when only 10% of tumors were diagnosed in such histological material. Thirty four percent of tumors were not macroscopically identified; all these inapparent tumors were advanced in 1987, whereas 53% were incipient in 1993. Moreover, inapparent tumors had a significantly lower degree of gallbladder wall infiltration and higher degree of differentiation. Well differentiated tumors had a lesser degree of wall infiltration. It is concluded that the careful histopathological study of gallbladder cancer has allowed a thorough knowledge of the natural history and clinical presentation of gallbladder carcinoma.

Adenocarcinoma↗

[Breast cancer and flow cytometry: comparative study of DNA ploidy pattern with clinicopathological parameters].

There is evidence that DNA quantization and histopathological classification of breast cancer may be useful for its therapeutic management. DNA flow cytometry, clinical and anatomopathological features of 60 paraffin embedded primary breast cancer tissue samples were studied. The aneuploidy percentage was 67%. There was a correlation between DNA index and degree of cellular pleomorphism, degree of differentiation and the fraction of cells in S phase. Likewise a correlation was found between the degree of cellular pleomorphism and the mitotic index. DNA cytophotometry was useful to solve cases of difficult diagnosis with flow cytometry ("near" diploid and tetraploid tumors). No correlation was found between aneuploidy, percentage of cells in phase S, degree of cellular atypia and mitotic degree with clinical stage, degree of lymph node involvement, tumoral size or age. It is suggested that these variables may have an independent behavior.

Adult↗

[Gallbladder carcinoma: expression of the c-myc and ras-p-21 oncogene products].

The expression of c-myc and p-ras-21 oncogenes was studied using an immunohistochemical method with monoclonal antibodies in 126 samples of gallbladder carcinoma (103 primary tumors and 23 metastatic lesions). Twenty five gallbladder samples without tumor evidence were used as controls. C-myc oncoprotein was positive in one control sample and p-ras-21 oncoprotein was negative in all. Among primary carcinomas c-myc was positive in 9 (9%) and p-ras-21 in 4 (4%); among metastatic carcinomas c-myc was positive in 6 (26%, p = 0.03 vs primary carcinoma) and p-ras-21 in 11 (48%, p < 0.001 vs primary carcinoma). There was a non significant association between c-myc and p-ras-21 expression and degree of histological differentiation and level of tumoral infiltration. It is concluded that c-myc and p-ras-21 oncoprotein expression is observed in less than 10% of primary gallbladder carcinomas and that this expression is significantly higher in metastatic carcinomas. This may reflect an activation or overexpression of these oncogenes in metastatic cells.

Amino Acid Sequence↗

[Mushroom poisoning in the IX region. Role of Amanita gemmata].

We report four episodes of mushroom poisoning that occurred between 1986 and 1990 in the province of Malleco. Twenty five of 36 individuals who ingested the mushroom became ill; they had an acute gastroenteritis that was followed in 7 by an acute hepatitis and in one by a massive upper gastrointestinal bleeding. Three subjects with fulminant hepatic failure and the subject with the massive bleeding died. Amanita gemmate (strain described as toxic in Chile since 1967) was found in two episodes and Amanita sp in one. The clinical picture is similar to that described for Amanita phaloides. The treatment is symptomatic but penicillin and silymarin may have an antitoxic action. The importance of warning the population about the existence of toxic mushrooms in Chile is emphasized.

Adult↗

[Determination of DNA content using cytophotometry in nuclear suspension conserved for prolonged periods (preliminary study)].

The variations in cytophotometric determination of DNA content were studied in a concentrated suspension of nuclei stored for prolonged periods. These came from normal and tumoral cells of an uterine leiomyosarcoma, fixed in formalin and included in paraffin. DNA was measured in normal and tumoral cells at days 0, 1, 7, 11, 19, 27 and 33. No significant variations in DNA measurement were observed. In a same day, there was an uniform DNA content, ploidy pattern and DNA index and an aneuploid pattern was diagnosed in all histograms. These results suggest that nuclear suspensions can be conserved for long periods and used for DNA content determination, allowing the access of remote places to these techniques.

Cytophotometry↗

Mutagenicity of blue rayon extracts of human bile in the Ames test.

The mutagenicity of human bile was examined in the Ames Salmonella/microsome assay. Bile samples were obtained from the gallbladders resected from patients with cholelithiasis, choledocholithiasis, gallbladder cancer, extrahepatic bile duct cancer and other diseases. For extraction of mutagenic components, the bile samples were treated with blue rayon and the adsorbed materials were assayed with Salmonella typhimurium TA98 in the presence of S9 mix. Twenty-four bile samples were tested and positive mutagenic activity was found in 14 samples. A 200-microliter bile equivalent material gave 6.3 times as many revertant colonies as the solvent control. With several samples that had undergone two cycles of blue rayon extraction, clear dose-response relationships in mutagenicity were demonstrated.

Adult↗

DNA content in gallbladder carcinoma: a flow cytometric study of 96 cases.

The DNA content in gallbladder carcinoma and its relation to histological and cytological features was studied in 79 primary gallbladder carcinomas and 16 metastases. Abnormal DNA content was observed in 48 (51%) of 95 cases. In primary carcinomas, 44 (55.6%) showed a diploid DNA content, and 35 (44.4%) were aneuploid. The majority of the metastatic lesions were aneuploid DNA (81.3%; P = 0.006). Marked differences in the coefficient of variation estimated by manual, Kosugi and Dean methods were detected (P = 0.005). Seventy-one per cent of early gallbladder carcinomas had a normal DNA content. In contrast 54% of the cases with subserosal or serosal infiltration had normal DNA content. In primary tumours the degree of architectural atypia had a close relationship with the degree of cellular atypia (P = 0.00001). Only two (15%) of 13 cases with mild architectural atypia, and 34 (51.5%) of 66 cases with marked architectural atypia were aneuploid. Only one (10%) of 10 cases with mild cellular atypia and 35 (51%) of 69 with high cellular atypia had abnormal DNA content (P = 0.01) The importance of DNA content as a marker in gallbladder carcinoma remains uncertain and its clinical importance requires further clinicopathological studies.

Adenocarcinoma, Papillary↗