Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastatic involvement of the breast is rare. The commonest cause is spread from a contralateral breast carcinoma. However, metastatic malignant melanoma, lymphoma and lung carcinoma have all been reported sporadically in the literature. Renal carcinoma is well recognised for its protean clinical manifestations ranging from loin pain, haematuria and an abdominal mass to less obvious metastatic effects such as pathological fracture of a long bone or one of a variety of associated paraneoplastic syndromes. We present a case of a renal carcinoma presenting with bilateral breast masses with literature review, and discuss the efficacy of the standard gamut of investigations in a breast mass of non-primary origin.
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PMID:Bilateral breast metastases from a renal carcinoma. 989 89

Prostate-specific membrane antigen (PSMA) is a type II integral membrane glycoprotein that was initially characterized by the monoclonal antibody (mAb) 7E11. PSMA is highly expressed in prostate secretory-acinar epithelium and prostate cancer as well as in several extraprostatic tissues. Recent evidence suggests that PSMA is also expressed in tumor-associated neovasculature. We examined the immunohistochemical characteristics of 7E11 and those of four recently developed anti-PSMA mAbs (J591, J415, and Hybritech PEQ226.5 and PM2J004.5), each of which binds a distinct epitope of PSMA. Using the streptavidin-biotin method, we evaluated these mAbs in viable prostate cancer cell lines and various fresh-frozen benign and malignant tissue specimens. In the latter, we compared the localization of the anti-PSMA mAbs to that of the anti-endothelial cell mAb CD34. With rare exceptions, all five anti-PSMA mAbs reacted strongly with the neovasculature of a wide spectrum of malignant neoplasms: conventional (clear cell) renal carcinoma (11 of 11 cases), transitional cell carcinoma of the urinary bladder (6 of 6 cases), testicular embryonal carcinoma (1 of 1 case), colonic adenocarcinoma (5 of 5 cases), neuroendocrine carcinoma (5 of 5 cases), glioblastoma multiforme (1 of 1 cases), malignant melanoma (5 of 5 cases), pancreatic duct carcinoma (4 of 4 cases), non-small cell lung carcinoma (5 of 5 cases), soft tissue sarcoma (5 of 6 cases), breast carcinoma (5 of 6 cases), and prostatic adenocarcinoma (2 of 12 cases). Localization of the anti-PSMA mAbs to tumor-associated neovasculature was confirmed by CD34 immunohistochemistry in sequential tissue sections. Normal vascular endothelium in non-cancer-bearing tissue was consistently PSMA negative. The anti-PSMA mAbs reacted with the neoplastic cells of prostatic adenocarcinoma (12 of 12 cases) but not with the neoplastic cells of any other tumor type, including those of benign and malignant vascular tumors (0 of 3 hemangiomas, 0 of 1 hemangioendothelioma, and 0 of 1 angiosarcoma). The mAbs to the extracellular PSMA domain (J591, J415, and Hybritech PEQ226.5) bound viable prostate cancer cells (LNCaP and PC3-PIP), whereas the mAbs to the intracellular domain (7E11 and Hybritech PM2J004.5) did not. All five anti-PSMA mAbs reacted with fresh-frozen benign prostate secretory-acinar epithelium (28 of 28 cases), duodenal columnar (brush border) epithelium (11 of 11 cases), proximal renal tubular epithelium (5 of 5 cases), colonic ganglion cells (1 of 12 cases), and benign breast epithelium (8 of 8 cases). A subset of skeletal muscle cells was positive with 7E11 (7 of 7 cases) and negative with the other four anti-PSMA mAbs. PSMA was consistently expressed in the neovasculature of a wide variety of malignant neoplasms and may be an effective target for mAb-based antineovasculature therapy.
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PMID:Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. 1039 65

Stereotactic radiosurgery (SR) is being used with increasing frequency in the treatment of brain metastases. This study provides data from a clinical experience with radiosurgery in the treatment of cases with multiple metastases and identifies parameters that may be useful in the proper selection and therapy of these patients. From January 1993 to April 1997, 97 patients (43 women and 54 men; median age 58 years) suffering from multiple brain metastases (median 3; range 2-4) in MRI scans, received SR with the Gamma Knife. The median dose at the tumor margin was 20 Gy (range 17-30 Gy). Median tumor volume was 3900 cmm (range 100-10,000). Different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness and ataxia had been the predominant neurological symptoms. Major histologies included lung carcinoma (44%), breast cancer (21%), renal cell carcinoma (10%), colorectal cancer (8%), and melanoma (7%). The median survival time was 6 months after SR. The actual one-year survival rate was 26%. In univariate and multivariate analysis, a higher Karnofsky performance rating and absence of extracranial metastases had a significantly positive effect on survival. Local tumor control was achieved in 94% of the patients. Complications included the onset of peritumoral edema (n = 5) and necrosis (n = 1). SR induces a significant tumor remission accompanied by neurological improvement and, therefore, provides the opportunity for prolonged high quality survival. We conclude that radiosurgical treatment of multiple brain metastases leads to an equivalent rate of survival when compared to the historic experience of patients treated with whole brain radiotherapy. Patients presenting initially with a higher Karnofsky performance rating and without extracranial metastases had a median survival time of nine months. Each such case should therefore be evaluated based on these factors to determine an optimal treatment regimen.
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PMID:Prognostic factor analysis for multiple brain metastases after gamma knife radiosurgery: results in 97 patients. 1042 Oct 75

Comparative allelotyping of the short arm of human chromosome 3 (3p) in four types of epithelial carcinomas was performed using an identical set of polymorphic markers. In total, 117 samples of non-papillary renal cell carcinoma (RCC), non-small cell lung carcinoma (NSCLC), carcinoma of uterine cervix (CC), and breast carcinoma (BC) were screened for loss of heterozygosity (LOH) with 10 di-, tri- and tetrameric markers covering nine bands of 3p. High LOH frequencies were detected in at least one locus: RCC (36/43, 84%), BC (20/26, 77%), NSCLC (16/24, 67%), and CC (15/24, 62%). Small interstitial deletions prevailed in BC and CC whereas large continuous and discontinuous deletions were mainly found in RCC and NSCLC. Different epithelial tumors displayed unique LOH profiles with partial overlaps in 3p26.1, 3p21.31, and 3p13. The overlap around D3S2409 (3p21.31) appeared common for RCC, BC and CC.
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PMID:Comparative allelotyping of the short arm of human chromosome 3 in epithelial tumors of four different types. 1043 10

Conjugates of the L49 monoclonal antibody (binds to the p97 antigen on melanomas and carcinomas) were formed by attaching Enterobacter cloacae beta-lactamase (bL) to the L49-Fab' fragment using a heterobifunctional cross-linking reagent or by linking the enzyme to L49-sFv using DNA recombinant technology. The conjugates thus formed, L49-Fab'-bL and L49-sFv-bL, were designed to activate cephalosporin containing anticancer prodrugs at the surfaces of antigen positive tumor cells. Results from in vitro experiments using two lung carcinoma cell lines demonstrated that the conjugates were equally active in effecting the release of phenylenediamine mustard from the cephalosporin nitrogen mustard prodrug CCM. While treatment with either of the conjugates combined with the maximum tolerated doses of CCM led to cures of established SN12P renal cell carcinoma tumors in nude mice, only the L49-sFv-bL conjugate maintained its ability to do so at 1/4 the maximum tolerated dose of CCM. L49-sFv-bL was also superior to L49-Fab'-bL in the 1934J renal cell carcinoma tumor model and was shown to be quite active in two in vivo models of human lung carcinoma. These results demonstrate that the recombinant fusion protein leads to more pronounced therapeutic windows than the chemical conjugate and is active in an array of human tumor models.
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PMID:Comparison of recombinant and synthetically formed monoclonal antibody-beta-lactamase conjugates for anticancer prodrug activation. 1056 79

We investigated the effects of UFT and its metabolites, GHB and GBL, on angiogenesis induced by tumor cells in a dorsal air sac (DAS) assay in mice. Five tumor cell lines (murine renal carcinoma; RENCA, human gastric cancer; 4-1ST, human small-cell lung carcinoma; LX-1, and human colon carcinoma; DLD-1, KM-20C) were used in the DAS assay. In this model, UFT demonstrated a significant anti-angiogenic activity in a dose-dependent manner while 5-FU (19 mg/kg/day) and 5'-DFUR (200 mg/kg/day) were less effective. Moreover, tegafur (FT), a component of UFT, and gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL), in vivo metabolites of UFT, inhibited angiogenesis induced by RENCA cells. The inhibitory effects of 5-FU, GHB, and GBL on angiogenesis were increased with administration by continuous infusion, providing a suitable pharmacokinetic profile. These results suggest that GHB and GBL are involved in the expression of anti-angiogenic activity of UFT.
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PMID:[Anti-angiogenic activities of UFT and its metabolites, GHB and GBL, in the dorsal air sac (DAS) model in mice]. 1066 Jul 38

Endobronchial metastases (EBM) secondaries to extrapulmonary solid malignant tumors are rare. Breast, colon and renal adenocarcinomas are the most frequent tumors associated with EBM. Since 1990 we have treated eight patients with EBM secondary to renal adenocarcinoma (three cases), colon adenocarcinoma (two cases), gastric adenocarcinoma (one case), bladder carcinoma (one case) and basal cell carcinoma (one case). Endobronchial lesions were detected by bronchoscopy and their metastatic nature was confirmed histopathologically in all eight cases. We also conducted a review of EBM reporting studies published in English language. The median interval from the diagnosis of the primary tumour was 41 months. Symptoms and radiological findings were indistinguishable from those of primary lung cancer. Five patients were treated with external radiotherapy with symptomatic improvement while two patients had chemotherapy and one patient underwent surgical resection of the metastasis. Systemic treatment was used in six cases with no significant effect on EBM. Median survival after EBM diagnosis was 9 months with one patient surviving 3.5 years and two patients still alive at 1 year. In conclusion, EBM usually represent a late manifestation requiring differential diagnosis from a primary lung cancer. Local treatment may result in symptomatic improvement but prognosis is generally poor averaging 1-2 years in most series.
Lung Cancer 2000 May
PMID:Endobronchial metastases secondary to solid tumors: report of eight cases and review of the literature. 1130 61

We report the efficient identification of four human histocompatibility leukocyte antigen (HLA)-A(*)0201-presented cytotoxic T lymphocyte (CTL) epitopes in the tumor-associated antigen PRAME using an improved "reverse immunology" strategy. Next to motif-based HLA-A(*)0201 binding prediction and actual binding and stability assays, analysis of in vitro proteasome-mediated digestions of polypeptides encompassing candidate epitopes was incorporated in the epitope prediction procedure. Proteasome cleavage pattern analysis, in particular determination of correct COOH-terminal cleavage of the putative epitope, allows a far more accurate and selective prediction of CTL epitopes. Only 4 of 19 high affinity HLA-A(*)0201 binding peptides (21%) were found to be efficiently generated by the proteasome in vitro. This approach avoids laborious CTL response inductions against high affinity binding peptides that are not processed and limits the number of peptides to be assayed for binding. CTL clones induced against the four identified epitopes (VLDGLDVLL, PRA(100-108); SLYSFPEPEA, PRA(142-151); ALYVDSLFFL, PRA(300-309); and SLLQHLIGL, PRA(425-433)) lysed melanoma, renal cell carcinoma, lung carcinoma, and mammary carcinoma cell lines expressing PRAME and HLA-A(*)0201. This indicates that these epitopes are expressed on cancer cells of diverse histologic origin, making them attractive targets for immunotherapy of cancer.
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PMID:Efficient identification of novel HLA-A(*)0201-presented cytotoxic T lymphocyte epitopes in the widely expressed tumor antigen PRAME by proteasome-mediated digestion analysis. 1113 22

Human tumor cells frequently exhibit abnormalities in the major histocompatibility complex (MHC) class I surface expression which can be due to structural alterations and/or dysregulation of various components of the MHC class I antigen processing machinery, such as HLA class I heavy and light chains, the peptide transporter and the proteasome subunits. Although several cofactors critical for proper MHC class I assembly have been identified, their contribution to the immune escape phenotype of tumor cells has not been analyzed. In order to determine whether tapasin deficits are an integral part of immune escape mechanisms of human tumors, we studied the constitutive and cytokine-regulated expression pattern of tapasin in malignant cells of distinct histology. Heterogeneous and reduced expression levels of tapasin were found in small-cell lung carcinoma, pancreatic carcinoma, colon carcinoma, head an neck squamous cell carcinoma and renal cell carcinoma cell lines. Tapasin downregulation was also prominent in surgically removed tumor lesions when compared to normal controls. The impaired tapasin expression is often associated with low MHC class I cell surface expression. In addition, various cytokines, including interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-4, but not granulocyte-macrophage colony stimulating factor (GM-CSF), transcriptionally upregulate to a distinct extent and in a time-dependent manner tapasin expression in tumor cells. Thus, deficient tapasin expression appears to be a frequent event in human tumor cells. Its restoration by cytokines further suggests that impaired tapasin expression in tumors is rather due to dysregulation than to structural alterations.
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PMID:Downregulation of the constitutive tapasin expression in human tumor cells of distinct origin and its transcriptional upregulation by cytokines. 1116 57

Mistletoe extracts have been used for decades for non-specific stimulation of the immune system in cancer therapy. Mistletoe lectins (ML) have been identified as the active principle with cytotoxic and immunomodulatory potencies. In the present in vivo experiments, the anticancer effects of an aqueous mistletoe extract (AME) were investigated in different subcutaneously growing syngeneic murine tumors such as Renca renal cell carcinoma, C8 colon 38 carcinoma, F9 testicular carcinoma, B16 melanoma and Lewis lung carcinoma. The animals used were immunocompetent mice of different strains (C57BL/6, BALB/c), depending on the type of tumor tested. After tumor transplantation, the mice were treated with AME at dose levels corresponding to 0, 0.3, 3, 30 or 300 ng ML/kg/d by the i.p. or s.c. route for a maximum of 4 consecutive weeks. The tumor volume was determined by serial caliper measurements and expressed relative to controls. Significant tumor growth inhibition was observed with the Renca , C8 colon 38 and F9 testicular carcinomas at 30 and 300 ng ML/kg/d. These findings were confirmed in independent repeat experiments. No inhibitory effects were seen with the Lewis lung carcinoma and B16 melanoma under the conditions described above. In conclusion, AME showed in vivo anticancer activity in different transplantable syngeneic murine tumor models following repeated parenteral treatment. In view of the low dose levels used, the effects are most likely due to the immunostimulatory rather than to the cytotoxic potencies of AME.
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PMID:Anticancer activity of an aqueous mistletoe extract (AME) in syngeneic murine tumor models. 1149 84


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