Keratin 19 mRNA measurement to detect micrometastases in lymph nodes in breast cancer patients

Schoenfeld, Mircea Ariel; Luqmani, Yunus A.; Sinnett, H. D.; Shousha, S; Coombes, R. Charles

doi:10.1038/bjc.1996.601

Cited by 50 publications

(19 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results concur with that of other groups in showing that MUC-1 is expressed in cells of lymphohaemopoetic origin (Hoon et al, 1995;Eltahir et al, 1998). Several studies in breast cancer have reported K19 to be a tissue-specific marker (Datta et al, 1994;Schoenfeld et al, 1994Schoenfeld et al, , 1996Schoenfeld et al, , 1997Noguchi et al, 1996a;Eltahir et al, 1998;Lockett et al, 1998). However, there is now a substantial body of evidence to show that K19 can also be detected in peripheral blood and lymphatic tissue rendering it unsuitable as a specific marker of submicroscopic disease (Adams et al, 1995;Burchill et al, 1995;Krismann et al, 1995;Denis et al, 1997;Dingemans et al, 1997).…”

Section: Discussionsupporting

confidence: 79%

“…Whilst lacking specific markers expressed by breast cancer cells a number of research groups have used cytokeratins 18 and 19, epithelial mucin (MUC1), carcinoembryonic antigen (CEA), CD 44 and maspin as transcript markers for the detection of submicroscopic metastases in lymph nodes, bone marrow or peripheral whole blood by reverse transcription PCR (RT-PCR) (Matsumura and Tarin, 1992;Datta et al, 1994;Gerhard et al, 1994;Noguchi et al, 1994Noguchi et al, , 1996aNoguchi et al, , 1996bSchoenfeld et al, 1994Schoenfeld et al, , 1996Schoenfeld et al, , 1997Brown et al, 1995;Mori et al, 1995;Gunn et al, 1996;Luppi et al, 1996;Yun et al, 1997;Eltahir et al, 1998;Lockett et al, 1998). However, there appears to be conflicting data regarding the specificity of some of these cell type specific markers in particular MUC-1 (Noguchi et al, 1994;Hoon et al, 1995), CD44 (Matsumura and Tarin, 1992;Eltahir et al, 1998) and K19 (Traweek et al, 1993;Schoenfeld et al, 1994Schoenfeld et al, , 1996Burchill et al, 1995;Krismann et al, 1995;Gunn et al, 1996;Dingemans et al, 1997;Yun et al, 1997;Eltahir et al, 1998). Maspin expression has been previously reported as being a specific marker for breast cancer (Luppi et al, 1996); however, there have been no larger confirmatory studies to assess the accuracy and reproducibility of these findings.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

et al. 1999

View full text Add to dashboard Cite

SummaryWe have developed sensitive assays for cytokeratin (K) 8, 16, 19, stromelysin 3 (ST3), MUC1 and maspin mRNAs using reverse transcription polymerase chain reaction (RT-PCR) and used these to assess lymph node status in patients undergoing surgery for breast cancer. In addition the RT-PCR assays were tested against lymph nodes from non-cancer patients to determine their specificity. Despite high sensitivity RT-PCR assays for K8, K16, K19, ST3 and maspin were not found to be useful as markers of submicroscopic disease as transcripts of these genes were detected in the great majority of control lymph nodes tested. Expression of MUC1 was also not found to be useful as it was both insensitive and non-specific. The importance of assessing potential markers against an adequately sized control population is demonstrated, as failure to do so can lead to erroneous conclusions.

show abstract

Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

et al. 1999

View full text Add to dashboard Cite

show abstract

“…This could al- 45 low the physician valuable lead time to alter either the combination of cytotoxic drugs or the form of the therapy. Attempts to devise methods of early detection of metastatic relapse have concentrated mainly on the development of very sensitive molecular assays for the detection of tumour-associated genes/proteins in circulating cells in the blood or micrometastases in the bone marrow [120][121][122] . The continual monitoring of cancer patients on therapy, for the traditional tumour markers such as carcino-embryonic antigen, has proved of limited use except in a few cancers; e.g.…”

Section: Putting Resistance To Good Usementioning

confidence: 99%

Mechanisms of Drug Resistance in Cancer Chemotherapy

Luqmani¹

2005

Med Princ Pract

543

357

View full text Add to dashboard Cite

The management of cancer involves procedures, which include surgery, radiotherapy and chemotherapy. Development of chemoresistance is a persistent problem during the treatment of local and disseminated disease. A plethora of cytotoxic drugs that selectively, but not exclusively, target actively proliferating cells include such diverse groups as DNA alkylating agents, antimetabolites, intercalating agents and mitotic inhibitors. Resistance constitutes a lack of response to drug-induced tumour growth inhibition; it may be inherent in a subpopulation of heterogeneous cancer cells or be acquired as a cellular response to drug exposure. Resistance varies. Although regulatory approval may require efficacy in as few as 20% of trial cohorts, a drug may subsequently be used in unselected patients displaying resistance to the treatment. Principal mechanisms may include altered membrane transport involving the P-glycoprotein product of the multidrug resistance (MDR) gene as well as other associated proteins, altered target enzyme (e.g. mutated topoisomerase II), decreased drug activation, increased drug degradation due to altered expression of drug-metabolising enzymes, drug inactivation due to conjugation with increased glutathione, subcellular redistribution, drug interaction, enhanced DNA repair and failure to apoptose as a result of mutated cell cycle proteins such as p53. Attempts to overcome resistance mainly involve the use of combination drug therapy using different classes of drugs with minimally overlapping toxicities to allow maximal dosages and with narrowest cycle intervals, necessary for bone marrow recovery. Adjuvant therapy with P-glycoprotein inhibitors and, in specific instances, the use of growth factor and protein kinase C inhibitors are newer experimental approaches that may also prove effective in abrogating or delaying onset of resistance. Gene knockout using antisense molecules may be another effective way of blocking drug resistance genes. Conversely, drug resistance may also be used to good purpose by transplanting retrovirally transformed CD34 cells expressing the MDR gene to protect the bone marrow during high-dose chemotherapy.

show abstract

“…One pg of cDNA synthesis product was amplified in a thermal cycler with Taq polymerase 2.5 U (Gibco) with 1 pM of forward/reverse primer for CNP (5'-ATGCATCTCTCCCAGCTGCT/3'-TACTCGC-CGGACCCTACAAT) and for GAPDH. Primers for GAPDH is synthesized as previously described [16]. The expected amplified products were 380 and 379 bp, respectively.…”

Section: Reverse Transcription-polymerase Chain Reactionmentioning

confidence: 99%

Shear stress induces expression of CNP gene in human endothelial cells

et al. 1995

View full text Add to dashboard Cite

To elucidate the effect of blood flow on gene transcription of C-type natriuretic peptide (CNP), human umbilical vein endothelial cells were exposed to shear stress in a cone-plate viscometer. Expression of CNP mRNA, evaluated by reverse transcriptiou-polymerase chain reaction, was markedly increased by exposure to shear stress of 24 dyne/cm 2 at 3 h. The CNP mRNA level was maintained until 12 h. Thus, the present study demonstrated for the first time that shear stress induces expression of CNP gene in human endothelial cells.

show abstract

Keratin 19 mRNA measurement to detect micrometastases in lymph nodes in breast cancer patients

Cited by 50 publications

References 10 publications

Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

Mechanisms of Drug Resistance in Cancer Chemotherapy

Shear stress induces expression of CNP gene in human endothelial cells

Contact Info

Product

Resources

About