Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of immune RNA treatment on the incidence of death from pulmonary metastases was studied in C57BL/6J mice after excision of a B16 murine melanoma. Immune RNA was extracted from the lymphoid tissues of guinea pigs immunized with B16 tumor and then incubated in vitro with normal C57BL/6J mouse splenocytes. Mice receiving intraperitoneal injections of these RNA-treated syngeneic splenocytes after the primary B16 isograft was resectioned showed significantly improved long-term survival (42 to 67 percent in three successive experiments) as compared to control mice (0 to 20 percent survival) receiving untreated splenocytes. The effect of RNA treatment was tumor-specific and ribonuclease sensitive. The results suggest that immunotherapy with immune RNA may be of benefit to certain patients after surgery for cancer.
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PMID:Prevention of death from metastases by immune RNA therapy. 69 19

We explored the state of the p53 gene in gastric cancer. Using one or more methods, we examined 15 specimens from primary carcinomas (14 tumors, one cell line), five cell lines derived from metastases, and seven paired samples of nonmalignant gastric mucosa. Sequence analyses of complementary DNA containing the entire p53 gene open reading frame demonstrated abnormalities in one of five samples from primary tumors and in all five samples from metastases. The single cell line derived from a primary carcinoma had no abnormality of the gene. The six abnormalities included four point mutations, one base-pair deletion resulting in a frame shift, and a 24 base-pair deletion caused by an intronic point mutation (as determined by sequence analysis of genomic DNA). Four of the six mutations mapped to regions highly conserved among species or involved in simian virus 40 T-antigen binding. Restriction fragment length polymorphism studies confirmed that chromosome 17p allelic deletions occur only in a minority of primary tumors, but that they may occur more frequently in metastases. Northern blotting and ribonuclease protection assays detected only a fraction of the p53 gene abnormalities detected by sequencing. Our findings indicate that mutations of the p53 gene are relatively rare in primary gastric tumors but appear to be relatively frequent in cell lines derived from metastatic lesions. Our results may help in understanding the molecular events associated with progression and metastasis in gastric carcinoma.
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PMID:Occurrence of p53 gene abnormalities in gastric carcinoma tumors and cell lines. 167 61

The mouse pancreatic amylase Amy-2.2 gene was fused to the structural gene for SV40 T antigen, and 51 independent transgenic founder mice carrying the fusion gene were generated. The majority of the founders and 100% of their offspring in the derived transgenic lines developed pancreatic acinar cell carcinomas and stomach carcinomas. Transgenic animals also had a high incidence of metastatic carcinomas in other tissues. The development of stomach carcinomas was unexpected because the Amy-2.2 promoter was not previously known to be expressed in stomach. Northern blot analyses and ribonuclease protection assays showed that Amy-2.2 is expressed in stomach, at approximately 0.05% of the level in pancreas. Expression of the fusion gene in stomach, therefore, appears to represent a previously unrecognized activity of the Amy-2.2 promoter. Examination of young transgenic mice demonstrated that preneoplastic lesions were present in pancreas and stomach before the development of neoplastic lesions in either tissue, consistent with the notion that stomach neoplasms are primary neoplasms and not metastases from the pancreas. Ribonuclease protection assays demonstrated that properly initiated large T and small t antigen transcripts were present in pancreas and stomach during tumorigenesis. T antigen protein was also detected in pancreas and stomach by immunohistochemistry. A time course for tumorigenesis was established for several transgenic mouse lines in which distinct types of lesions appeared at predictable times. This study provides the basis for future analysis of the role of SV40 T antigen in the progression and maintenance of pancreatic and stomach carcinomas.
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PMID:Transgenic mice carrying a murine amylase 2.2/SV40 T antigen fusion gene develop pancreatic acinar cell and stomach carcinomas. 170 90

Drug resistance is one of the major impediments to the treatment of advanced neuroblastoma. Two neuroblastoma cell lines established from the same patient before (KP-N-AY) and after (KP-N-AYR) chemotherapy are described. Both cell lines were established from bone-marrow metastases of a 2 1/2-year-old patient with stage IV neuroblastoma. Chromosomal analysis, catecholamine assessment and the surface membrane phenotype of these cell lines confirmed that the tumors were of neuroblastoma origin. Compared with the KP-N-AY cell line, the KP-N-AYR line had decreased N-myc amplification but increased N-myc expression. An in vitro sensitivity test using a clonogenic assay showed the KP-N-AYR cell line to be 3.0-fold resistant to adriamycin and 2.7-fold resistant to cis-platinum as compared with the KP-N-AY cell line. The expression of the multi-drug-resistance gene (MDR1) was not observed in either cell line by the ribonuclease protection assay. The KP-N-AY cell line revealed only faint MDR1 RNA by the polymerase chain reaction, whereas the KP-N-AYR cell line had no expression of the MDR1 gene. The level of glutathione-S-transferase-pi was significantly higher in the KP-N-AYR cell line than in the KP-N-AY cell line. These findings suggest that the development of clinical drug resistance may be associated with the enhanced glutathione-S-transferase-pi activity but not with MDR1 gene expression.
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PMID:Different drug sensitivity in two neuroblastoma cell lines established from the same patient before and after chemotherapy. 200 54

In the last decades several markers of pancreatic neoplasia have been proposed to obtain a diagnosis as earlier as possible. Prerequisites of a good tumor marker are high sensitivity and specificity. Among the various substances, serum determination of pancreatic enzymes has been found of no utility in early diagnosis of pancreatic cancer, due to its lack in sensitivity and specificity. Similar results with ribonuclease and deoxyribonuclease. Oncofetal antigens (CEA and POA) have been initially considered promising indices; however, further studies showed their limits. In particular CEA is greatly influenced by the presence of hepatic metastases; therefore, serum levels are detectable only in advanced stages. TPA is characterized by a high sensitivity, but lacks in specificity and its use is now avoided. A real progress in the field of tumor markers has been made in the last years with the monoclonal antibody technique: among them CA 19-9 showed a good sensitivity and a satisfactory specificity as regards the diagnosis of pancreatic cancer. However, it cannot be considered as absolute aid, since it is influenced by several factors, as tumor spread, jaundice and liver dysfunction.
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PMID:[Value and limitations of neoplasm markers in the diagnosis of pancreatic carcinoma]. 204 59

Urinary excretion of alpha-glucosidase (AGL), gamma-glutamyltransferase (GGT) and ribonuclease (RNase), and serum amylase and immunoreactive trypsin (IRT) were determined in 38 control subjects, 48 patients with pancreatic cancer, 77 with chronic pancreatitis and 47 with extrapancreatic diseases in order to ascertain the presence of a renal tubular damage and to investigate its etiology. A significantly increased frequency of pathological results for all urinary enzymes was documented in the various groups of patients as compared to controls. Significant correlations were detected among AGL, GGT and RNase. Considering the subjects as a whole, GGT and RNase excretions correlated with serum IRT and amylase; the two urinary enzymes were found to be higher when jaundice was present. In chronic pancreatic disease enzymuria was related to increased serum pancreatic enzymes; in extrapancreatic diseases it was associated to hyperbilirubinemia. The vast majority of patients with pancreatic cancer and elevated urinary enzymes presented hepatic metastases and/or jaundice. We can conclude that an anatomical and functional tubular impairment is detectable in some patients with chronic pancreatic and extrapancreatic diseases. Tubular damage seems to least in part to be related to pancreatic inflammation and necrosis in chronic pancreatic disease, while jaundice may be found to play an important role in diseases of the hepatobiliary tract. In pancreatic cancer, liver dysfunction (presence of liver metastases and/or extrahepatic cholestasis) also appears to be involved in altering tubular cells.
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PMID:Renal tubular dysfunction in pancreatic cancer and chronic pancreatitis. 256 74

The influence of a variety of clinical and biochemical parameters on the activities in serum of ribonuclease (RNAse) selective for polycytidylic acid (RNAse C) were examined in 90 adult patients with cancer. The clinical data base determined on each patient included: RNAse C level, carcinoembryonic antigen (CEA) level, age, sex, race, presence (or absence of metastases, type of cancer, site of metastasis, renal function blood urea nitrogen [BUN], creatinine), hepatic function (bilirubin, alkaline phosphatase), and nutritional status (percent ideal body weight, percent weight loss, and albumin). Common tumor types studied included: colon (21), lung (18), breast (15), and hepatocellular carcinoma (10). For comparison, 175 nonmalignant control patients were studied to establish the normal range for RNAse. In patients with cancer, RNAse levels were increased in 57% and CEA levels were above 10 ng/dl in 36%. Although patients with BUN greater than 25 mg/dl or creatinine greater than 1.5 mg/dl were not entered on the study, nonetheless, RNAse was significantly (P less than 0.05) associated with both BUN and creatinine. Nutritional status also had an important influence on RNAse levels as both percent weight loss and percent ideal body weight were significantly (P less than 0.05) associated with circulatory RNAse: weight loss resulted in higher RNAse levels. These results account in part for the increased RNAse levels seen in those malignant conditions such as pancreatic and lung cancer commonly associated with weight loss in advanced stage. The possibility that circulatory RNAse C determination will provide a sensitive means for assessing nutritional status in cancer patients will require prospective evaluation.
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PMID:Influence of nutritional status on circulatory ribonuclease C levels in patients with cancer. 298 Nov 45

The tumor markers Ca 125 and serum ribonuclease were determined simultaneously in 35 patients with primary ovarian cancer during therapy and follow-up. In patients with second-look operation, Ca 125 and ribonuclease correlated well with the presence of metastases. In our experience the marker Ca 125 appeared to be superior to serum ribonuclease levels. Recurrence may be detected equally well with both markers.
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PMID:[Experiences with the tumor markers Ca 125 and plasma ribonuclease in ovarian cancer]. 348 39

12 women with primary breast cancer underwent somatostatin receptor scintigraphy (SRS) with 111In-DTPA-D-Phe1-octreotide. The tumour sizes varied between 2 and 5 cm and were all, except one, palpable at clinical examination. Tumour biopsies were taken with additional sampling from normal breast tissue, fat, muscle, axillary lymph nodes and peripheral blood. Ratios between the 111In activity concentration in the tissue biopsies (Ti) and in peripheral blood (B) as well as in normal breast tissue (Br) were calculated. In 8/12 patients the scintillation detector was used intraoperatively for radioactivity measurements of the biopsies in situ and ex vivo. The sstr-subtype profiles were determined by northern blot analysis and the relative expression of sstr2 by ribonuclease protection assay (RPA) and immunocytochemistry. Preoperative SRS visualised all primary breast cancer tumours. The scintigraphic image showed no correlation with the histopathological type of the tumour or with the abundance of oestrogen/progesterone receptors on the tumour. Two patients with a massive tumour infiltration of the lymph nodes had a distinct positive SRS of the ipsilateral axilla. In one patient with three nodal metastases the scintigraphic image of the axilla was weak but visible. Four other patients with a negative axillary scintigraphy had 1-2 lymph node metastases. The Ti/B ratios for the breast tumours varied between four and 33 and were not different from Ti/Br ratios. In lymph node metastases the Ti/B ratios were higher (10-41). Intraoperative detector measurements showed a significant difference between the breast tumour and normal tissue in 2/8 patients in situ. Similar measurements on excised tissues (ex vivo) showed a significant difference in 6/8 patients. Two patients with lymph node metastases exhibited a significantly increased uptake ex vivo by detector measurements, but in only one of them in situ. All tumour biopsies expressed the presence of sstrl, 3, 4 and 5, but not of sstr2 at northern analysis. On the other hand, sstr2 was detected in all tumours by RPA and immunocytochemistry. Preoperative SRS visualised primary breast cancer lesions in all 12 patients. SRS could also demonstrate extensive axillary tumour infiltration. Intraoperative use of the scintillation detector could not exclude axillary metastases in situ. The low Ti/B values of both primary tumours and metastases indicate limitations of the radiopharmaceutical used.
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PMID:Indium-111-octreotide scintigraphy, intraoperative gamma-detector localisation and somatostatin receptor expression in primary human breast cancer. 1218 70

Chemokines promote tumour progression by enhancing proliferation and modifying the immune response. The purpose of this study was to test the hypothesis that CCL2 monocyte chemotactic protein-1 (MCP-1) contributes to the progression of colorectal cancer by influencing the number and distribution of tumour associated macrophages (TAMs). Chemokine expression was assessed in human colorectal adenocarcinomas by ribonuclease protection assay (RPA). Colonic adenocarcinoma cell lines were used to assess chemokine production by enzyme linked immunosorbant assay (ELISA), and Boyden microchemotaxis assays were performed to determine cell line supernatant monocyte chemotactic activity. CCL2 production was assessed in paraffin embedded tumour samples by immunohistochemistry. Finally, the number of macrophages and their distribution was determined in the same colorectal adenocarcinomas and compared with CCL2 expression and tumour stage. Results showed that CCL2 produced by cell lines induced monocyte chemoattraction, the expression of this chemokine in solid cancers increased with tumour stage (P < 0.05) and immunohistochemistry localized production to tumour cells. Analysis of the macrophage infiltrate showed that the accumulation was significantly greater in tumours than controls (P < 0.005) and within tumours it was greatest in necrotic regions (median 44,600 per mm(3)). Macrophage accumulation increased with tumour stage and correlated with CCL2 expression (r(s) = 0.8). CXCL8 interleukin 8 (IL-8), a potent angiogenic factor and growth factor, was expressed in all tumours and cell lines. It is concluded that CCL2 induces the accumulation of tumour promoting TAMs in human colorectal cancer and represents a therapeutic target to modify the macrophage response and direct immune mediated therapy.
Clin Exp Metastasis 2007
PMID:Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer. 1739 Jan 11


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