Original Article
bcl-2 Protein in Non-Small-Cell Lung Carcinoma
N Engl J Med 1993; 329:690-694September 2, 1993
- Abstract
Background
The proto-oncogene bcl-2 encodes a protein that inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but no data are available on the frequency or clinical importance of its expression in carcinoma. We studied bcl-2 expression in patients with non-small-cell lung carcinoma and correlated this phenomenon with survival.
Methods
Immunochemical analysis with a monoclonal antibody specific for bcl-2 was used to detect the protein in tumor samples from 122 patients undergoing surgery for squamous-cell carcinoma (80 patients) or adenocarcinoma (42 patients). The possibility that bcl-2 expression correlated with survival was investigated with use of the log-rank test, hazard ratios, and their confidence intervals.
Results
We detected bcl-2 protein in 25 percent of squamous-cell carcinomas (20 of 80) and 12 percent of adenocarcinomas (5 of 42). In adjacent normal respiratory epithelium, bcl-2 was expressed only in basal cells. Survival at five years was higher among patients with bcl-2-positive tumors, both in the group as a whole (P<0.1) and in the group with squamous-cell carcinoma (P<0.02). Patients 60 years of age or older who had bcl-2-positive tumors had the best prognoses, both in the group as a whole (P<0.02) and in the group with squamous-cell carcinoma (P<0.01).
Conclusions
The proto-oncogene bcl-2 is abnormally expressed in some lung carcinomas, and its expression may have prognostic importance.
Media in This Article
Figure 1
Immunostaining of Lung Tissue with a Monoclonal Antibody Specific for bcl-2 (Alkaline Phosphatase:Anti-Alkaline Phosphatase Method, with Hematoxylin Counterstaining).Figure 2
Survival of Patients with Non-Small-Cell Lung Carcinoma and the Subgroup 60 Years Old or Older, According to Status for bcl-2 Protein.Article Activity
- Article
The bcl-2 proto-oncogene is involved in the 14;18 translocation,1 a chromosomal abnormality present in 70 percent of follicular lymphomas and 20 percent of diffuse B-cell lymphomas2,3. In this translocation4 the bcl-2 gene is juxtaposed with the immunoglobulin heavy-chain gene on chromosome 14 and is brought under the control of the promoter of this gene. In consequence, abnormally high levels of bcl-2 protein are produced1,5,6. This protein protects cells from programmed cell death (apoptosis),7 as shown by the survival advantage of cells in which expression of the gene has been artificially induced (e.g., by the creation of transgenic mice or by cell transfection)8,9.
Korsmeyer has recently proposed10 that bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death. So far, it is the only gene belonging to this category that has been identified. It has an oncogenic effect because of a gain of function (i.e., expression of the protein when it should not be present) and appears to lead to neoplastic growth at a rate slower than that of growth induced by oncogenes directly affecting cell proliferation11.
Hockenbery et al.11 have reported that bcl-2 is expressed not only in lymphoid cells but also in several epithelial tissues -- e.g., skin and intestine -- where it is detectable in basal cells but not in more superficial, differentiated cells. It has been suggested that this pattern of expression assists the survival of stem cells while preventing the overaccumulation of differentiated cells10. This implies that if bcl-2 expression were to persist in epithelial cells in which the protein should no longer be present, such cells would accumulate abnormally. This would provide a potential mechanism for neoplastic-cell growth, but to the best of our knowledge, no studies of bcl-2 expression in carcinoma have been performed. To address this question we studied lung cancer, which accounts for approximately one quarter of all deaths due to cancer in industrialized countries12. We evaluated a series of 122 patients with non-small-cell carcinomas of the lung for whom detailed information on long-term follow-up was available. We intended to establish whether bcl-2 protein is expressed in these tumors and to study its relation to survival.
Methods
Tissue Samples
Freshly frozen samples of lung specimens from 122 patients undergoing resection for primary lung cancer were obtained from diagnostic histopathology laboratories at the John Radcliffe Hospital, Oxford. Frozen samples were stored at -70 °C until studied.
Patients
Table 1Table 1
Characteristics of 122 Patients Undergoing Resection for Non-Small-Cell Lung Carcinoma, According to Type of Cancer and Status for bcl-2 Expression. shows the characteristics of the 122 patients in whom bcl-2 expression was studied, and Table 2Table 2
Characteristics of 115 Patients with Non-Small-Cell Lung Carcinoma in Whom Survival Was Studied in Relation to bcl-2 Expression. those of the 115 patients in whom survival was analyzed according to their status for bcl-2. All patients underwent surgery if their tumor was apparently limited to one lobe, with no evidence of metastasis, and their residual lung function was good. The pathological stages of the tumors were T1, T2, N0, and N1 of the TNM classification (Table 1 and Table 2), corresponding to stages I and II of the classification used by the American Joint Committee for Cancer Staging and Reporting13 and stages I and II of the International Staging System for Lung Tumours14. Although clinical follow-up was available for all patients, seven who died within 30 days after surgery (perioperative mortality) were excluded from survival analysis. The 115 patients included had no other form of cancer. No chemotherapy or radiotherapy was given before the surgery, which represented the sole treatment in most patients. Local radiotherapy was given at later dates to control symptoms in four patients with squamous-cell carcinoma and five with adenocarcinoma. Chemotherapy was given to one patient with adenocarcinoma.Follow-up of the 115 patients included in the survival analysis ranged from 50 to 2282 days (76 months), with a median of 1033 days (34 months). Fifty-two patients died during follow-up; the 63 alive at the time of study were followed for 50 to 2282 days (76 months), with a median of 1448 days (48 months). Statistical analysis was performed for the patients as a whole and for the group with squamous-cell carcinoma, but not for the group with adenocarcinoma since bcl-2 was expressed in only five patients in this group.
Histopathological and Immunohistologic Examination
Diagnosis was based on conventional morphologic examination of paraffin-embedded specimens. Tumors were classified as squamous-cell carcinomas or adenocarcinomas according to the predominant cell type. Staining was performed on cryostat sections with the alkaline phosphatase:anti-alkaline phosphatase procedure as previously described,15 with use of a monoclonal antibody specific for bcl-2 (clone 100)16. Staining without this antibody was routinely performed as a negative control procedure.
Statistical Analysis
Survival was measured in days from the date of surgery. Patients were grouped according to their age at the time of the surgery, as being either less than 60 years old or 60 years old or older, as described in previous studies of lung cancer17,18. Actuarial survival curves were plotted with the method of Kaplan and Meier19. Two-sided P values were determined with the log-rank test,20 and the death hazard ratio with a 95 percent confidence interval was calculated as described by Machin and Gardner21. The association between bcl-2 expression and the grade of tumor differentiation, the T stage, and the N stage was investigated by a frequency table22. The homogeneity of age in different groups was assessed by calculating the value of F with one-way analysis of variance23. Cox regression analysis was performed with use of the SAS statistical package (SAS Institute, Cary, N.C.).
Results
Immunostaining for bcl-2 Protein
Of the 122 patients studied (80 with squamous-cell carcinomas and 42 with adenocarcinomas), 25 (20 percent) were found to have bcl-2 protein (Figure 1AFigure 1
Immunostaining of Lung Tissue with a Monoclonal Antibody Specific for bcl-2 (Alkaline Phosphatase:Anti-Alkaline Phosphatase Method, with Hematoxylin Counterstaining).). The findings are presented according to the histologic type of carcinoma in Table 1. In areas of normal epithelium adjacent to the tumor, basal cells showed positive staining for bcl-2 but the more differentiated columnar cells remained negative (Figure 1B).Survival and Expression of bcl-2
The study results are summarized in Table 3Table 3
Survival of 115 Patients with Non-Small-Cell Lung Carcinoma, According to Type of Tumor, Age, and Status for bcl-2 Expression.. There was no association of bcl-2 expression with the grade of tumor differentiation (P>0.2), the T stage (P>0.2), or the N stage (P>0.2), either among the patients as a whole or in the group with squamous-cell carcinoma. The distribution of ages was homogeneous when age was analyzed independently of bcl-2 status (Table 2). Overall, there was only a slight difference in survival between the patients with bcl-2-negative tumors and those with bcl-2-positive tumors (P<0.1) (Figure 2Figure 2Survival of Patients with Non-Small-Cell Lung Carcinoma and the Subgroup 60 Years Old or Older, According to Status for bcl-2 Protein.). Cox regression analysis (Table 4Table 4
Value of Six Variables in Predicting Survival in 115 Patients with Non-Small-Cell Lung Carcinoma, According to Cox Regression Analysis.) confirmed that this difference in survival was not significant and that the only significant prognostic factor was the involvement of regional lymph nodes by tumor. In the patients with bcl-2-negative tumors, the hazard ratio was 1.92 (95 percent confidence interval, 1.08 to 3.6); in those with bcl-2-negative tumors who were 60 years old or older, the ratio was higher -- 2.59 (95 percent confidence interval, 1.26 to 5.31; P<0.02) (Figure 2). No correlation between the expression of bcl-2 and survival was evident in the group of younger patients (Table 3).When the patients with squamous-cell carcinoma were studied separately, the association between bcl-2 expression and survival was more evident (P<0.05). Cox regression analysis (Table 5Table 5
Value of Six Variables in Predicting Survival in 75 Patients with Squamous-Cell Lung Carcinoma, According to Cox Regression Analysis.) showed that a patient's status for bcl-2 had the lowest P value (P = 0.010) and was a better predictor of survival than status for regional-node involvement (P = 0.033). In the patients 60 years old or older, the association was also significant (P<0.01) (Figure 3Figure 3
Survival of Patients with Squamous-Cell Lung Carcinoma and the Subgroup 60 Years Old or Older, According to Status for bcl-2 Protein. and Table 3); no evidence of such an association was found in the younger patients. There were too few patients with bcl-2-positive tumors (five patients) in the group with adenocarcinoma to allow statistical analysis of this diagnostic group.Discussion
Immunostaining of tumors from patients undergoing surgical resection for lung cancer revealed bcl-2 expression in both squamous-cell carcinomas and adenocarcinomas. Both these types of tumors are believed to originate from the respiratory epithelium, although the pattern of expression of bcl-2 protein is quite different from that seen in normal bronchial mucosa (and indeed in any other epithelium examined),11 in which the basal cells stain for bcl-2 but well-differentiated cells do not. This suggests that the homogeneous staining in bcl-2-positive tumors reflects a persistence of bcl-2 expression that was not suppressed as the neoplastic cell differentiated.
The cause of this abnormal expression of bcl-2 in lung tumors is unknown. The classic cause of overexpression of bcl-2 -- the 14;18 translocation -- has not been detected in lung carcinoma, nor have other abnormalities of chromosome 18. However, it is worth noting that since this protein can be overexpressed in some follicular lymphomas without the 14;18 translocation,24 this cytogenetic abnormality is not the sole cause of bcl-2 deregulation in neoplastic cells. The finding that the protein is absent or weakly expressed in proliferating lymphocytes,16 although bcl-2 messenger RNA increases in peripheral-blood lymphocytes after in vitro stimulation,25 suggests post-transcriptional regulation as a possible physiologic mechanism controlling the expression of bcl-2. If this is so, alterations in the control of messenger RNA translation could lead to aberrant accumulation of bcl-2 protein.
Two important questions follow the demonstration of an abnormally expressed antigen in tumors: what value may the antigen have as a diagnostic marker, and how is it related to survival26? The finding that bcl-2 is absent in normal well-differentiated epithelial cells but present in a number of lung carcinomas suggests that its detection in differentiated epithelial cells could be an indicator of malignancy. However, the value of bcl-2 detection as a diagnostic tool remains uncertain, and before considering its expression in differentiated epithelial cells to be a marker of this sort, one must know whether bcl-2 expression occurs not only in fully transformed neoplastic cells but also occasionally in dysplastic and metaplastic cells.
We propose that expression of bcl-2 protein may be a new prognostic marker in non-small-cell carcinoma of the lung, in addition to blood-group antigen A,17 blood-group-antigen-related carbohydrates,18 and (only in adenocarcinoma) K-ras oncogene mutation27. In our study, the death hazard ratio was higher in patients with bcl-2-negative tumors, whether we evaluated all patients or only those with squamous-cell carcinoma, and the log-rank tests showed that bcl-2 expression was significantly associated with survival in the group with squamous-cell tumors. Furthermore, Cox regression analysis revealed that bcl-2 status was a stronger predictor of survival than status for lymph-node involvement in the patients with squamous-cell carcinomas, all of whom had disease no further advanced than stage T2N1. Analysis according to age revealed that this result appeared to be due to a better prognosis among patients 60 years old or older with bcl-2-positive tumors. Because of the relatively small number of patients studied, the confidence intervals for the death hazard ratios were wide, indicating that these data must be interpreted with caution21,28 and require confirmation by study of a larger series. Nevertheless, when patients 60 years old or older were considered, the 95 percent confidence interval indicated that the true value of the death hazard ratio at five years would very likely be higher in patients with bcl-2-negative tumors. This result strongly suggests the hypothesis, supported by the log-rank analysis, that these patients with bcl-2-positive tumors do have a better clinical outcome, and should prompt further investigation of bcl-2 as a prognostic marker in lung cancer. Should carcinomas that might otherwise be regarded as inoperable be reconsidered for surgical treatment if biopsy shows them to be positive for bcl-2? To answer this question, we think that the analysis of bcl-2 expression in biopsy specimens from patients whose tumors are classified as inoperable at present, and the correlation of expression with survival, would be of great value.
Why bcl-2 expression appears to be associated with less aggressive tumor behavior remains to be clarified. However, it is known that bcl-2 promotes cell survival even when the rate of cell proliferation is not high, providing a growth advantage that may eventually lead to neoplastic transformation9. It has been suggested that in clones in which a low mitotic rate is offset by bcl-2 expression, the rate of acquiring complementary defects is slower than in clones with a high mitotic rate8. A growth advantage due to cellular survival with a low mitotic rate, together with slower acquisition of additional genetic defects, could explain the indolent progression of follicular lymphoma, in which bcl-2 expression is a frequent primary aberration8,9. Korsmeyer has recently suggested that alterations of a gene such as bcl-2, which controls cell death, could be a frequent primary aberration not limited to follicular lymphoma but occurring in other types of neoplasms10. Our observation of a group of bcl-2-positive lung cancers with relatively slow progression suggests that perhaps in these tumors, bcl-2 expression acts as an initial oncogene, as in follicular lymphomas, leading to less aggressive growth of tumors.
We conclude that bcl-2 is abnormally expressed in some non-small-cell lung carcinomas. Further investigations are called for to elucidate its possible use as a diagnostic and prognostic marker in the management of these tumors.
Supported by the Leukaemia Research Fund, the Imperial Cancer Research Fund, and the Cancer Research Campaign. Dr. Pezzella is a Leukaemia Research Fund research fellow.
We are indebted to Dr. Raymond G. Flood for his statistical advice and critical review of the manuscript; to Mrs. Margaret Jones and Mr. Geoffrey Richardson for their technical assistance; and to the cardiothoracic surgeons at Oxford, Mr. A. Gunning, Mr. S. Westaby, and Mr. R. Pillai, for their continuing assistance in providing specimens.
Source Information
From the Leukaemia Research Fund Immunodiagnostics Unit (F.P., D.Y.M.), the Nuffield Department of Pathology (H.T., I.K., M.F.T., M.S.D., K.C.G.), the University Data Centre (C.B.P.), and the Molecular Oncology Laboratory (Imperial Cancer Research Fund) (A.H.), John Radcliffe Hospital, Oxford, United Kingdom.
Address reprint requests to Dr. Pezzella at the Leukaemia Research Fund Immunodiagnostics Unit, Level 1, Maternity Block, John Radcliffe Hospital, OX3 9DU, Oxford, United Kingdom.
- References
References
1
Tsujimoto Y ,Croce CM . Analysis of the structure, transcripts and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci U S A 1986;83:5214-5218
CrossRef | Web of Science | Medline2
Pezzella F ,Ralfkiaer E ,Gatter KC ,Mason DY . The 14;18 translocation in European cases of follicular lymphoma: comparison of Southern blotting and the polymerase chain reaction. Br J Haematol 1990;76:58-64
CrossRef | Web of Science | Medline3
Aisenberg AC ,Wilkes BM ,Jacobson JO . The bcl-2 gene is rearranged in many diffuse B-cell lymphomas. Blood 1988;71:969-972
Web of Science | Medline4
Tsujimoto Y ,Finger LR ,Yunis J ,Nowell PC ,Croce CM . Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 1984;226:1097-1099
CrossRef | Web of Science | Medline5
Tsujimoto Y ,Ikegaki N ,Croce CM . Characterization of the protein product of bcl-2, the gene involved in human follicular lymphoma. Oncogene 1987;2:3-7
Web of Science | Medline6
Cleary ML ,Smith SD ,Sklar J . Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 1986;47:19-28
CrossRef | Web of Science | Medline7
Hockenbery D ,Nunez G ,Milliman C ,Schreiber RD ,Korsmeyer SJ . Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990;348:334-336
CrossRef | Web of Science | Medline8
McDonnell TJ ,Deane N ,Platt FM , et al. bcl-2-Immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell 1989;57:79-88
CrossRef | Web of Science | Medline9
Vaux DL ,Cory S ,Adams JM . Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988;335:440-442
CrossRef | Web of Science | Medline10
Korsmeyer SJ . Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood 1992;80:879-886
Web of Science | Medline11
Hockenbery DM ,Zutter M ,Hickey W ,Nahm M ,Korsmeyer SJ . BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci U S A 1991;88:6961-6965
CrossRef | Web of Science | Medline12
McVie JG. Cancer of the lung and pleura. In: Hossfeld DK, Sherman CD, Love RR, Bosch FX, eds. Manual of clinical oncology. 5th ed. Berlin, Germany: Springer-Verlag, 1990:217-27.
13
Carr DT, Mountain CF. Staging lung cancer. In: Strauss MJ, ed. Lung cancer: clinical diagnosis and treatment. New York: Grune & Stratton, 1983:201-12.
14
Mountain CF . A new international staging system for lung cancer. Chest 1986;89:Suppl:225S-233S
Web of Science | Medline15
Cordell JL ,Falini B ,Erber WN , et al. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 1984;32:219-229
CrossRef | Web of Science | Medline16
Pezzella F ,Tse AG ,Cordell JL ,Pulford KA ,Gatter KC ,Mason DY . Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation. Am J Pathol 1990;137:225-232
Web of Science | Medline17
Lee JS ,Ro JY ,Sahin AA , et al. Expression of blood-group antigen A -- a favorable prognostic factor in non-small-cell lung cancer. N Engl J Med 1991;324:1084-1090
Full Text | Web of Science | Medline18
Miyake M ,Taki T ,Hitomi S ,Hakomori SI . Correlation of expression of H/Ley/Lb antigens with survival in patients with carcinoma of the lung. N Engl J Med 1992;327:14-18
Full Text | Web of Science | Medline19
Kaplan EL ,Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481
CrossRef | Web of Science20
Peto R ,Pike MC ,Armitage P , et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Br J Cancer 1977;35:1-39
CrossRef | Web of Science | Medline21
Machin D, Gardner MJ. Calculating confidence intervals for survival time analyses. In: Gardner MJ, Altman DG, eds. Statistics with confidence: confidence intervals and statistical guidelines. London: British Medical Journal, 1989:64-70.
22
Altman DG. Comparing groups: categorical data. In: Altman DG. Practical statistics for medical research. London: Chapman & Hall, 1991:229-76.
23
Comparison of several groups. In: Armitage P, Berry G. Statistical methods in medical research. 2nd ed. Oxford, England: Blackwell, 1987:186-213.
24
Pezzella F ,Gatter KC ,Mason DY , et al. Bcl-2 protein expression in follicular lymphomas in absence of 14;18 translocation. Lancet 1990;336:1510-1511
CrossRef | Web of Science | Medline25
Reed JC ,Tsujimoto Y ,Alpers JD ,Croce CM ,Nowell PC . Regulation of bcl-2 proto-oncogene expression during normal human lymphocyte proliferation. Science 1987;236:1295-1299
CrossRef | Web of Science | Medline26
Lee JS ,Hong WK . Prognostic factors in lung cancer. N Engl J Med 1992;327:47-48
Full Text | Web of Science | Medline27
Slebos RJC ,Kibbelaar RE ,Dalesio O , et al. K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 1990;323:561-565
Full Text | Web of Science | Medline28
Bailar JC III, Mosteller F, eds. Medical uses of statistics. 2nd ed. Boston: NEJM Books, 1992.
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CrossRef2
Y.-L. Tsai, Z.-F. Wang, W.-W. Chen, T.-C. Chang. (2011) Emulsified BMVC derivative induced filtration for G-quadruplex DNA structural separation. Nucleic Acids Research 39:17, e114-e114
CrossRef3
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CrossRef4
In-Hyuk Lee, So-Young Choi, Ji-Hoon Park, Chin-Soo Kim. (2011) Expression of Bcl-2 in the epithelial lining and clinical findings of keratocystic odotogenic tumor. Journal of the Korean Association of Oral and Maxillofacial Surgeons 37:3, 161
CrossRef5
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CrossRef6
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CrossRef7
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CrossRef8
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CrossRef11
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CrossRef12
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CrossRef14
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CrossRef15
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CrossRef16
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CrossRef17
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CrossRef19
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CrossRef20
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CrossRef21
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CrossRef23
S Hoffarth, A Zitzer, R Wiewrodt, P S Hähnel, V Beyer, A Kreft, S Biesterfeld, M Schuler. (2008) pp32/PHAPI determines the apoptosis response of non-small-cell lung cancer. Cell Death and Differentiation 15:1, 161-170
CrossRef24
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CrossRef25
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CrossRef26
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CrossRef27
Justin L. Mott, Gregory J. Gores. (2007) Piercing the armor of hepatobiliary cancer: Bcl-2 homology domain 3 (BH3) mimetics and cell death. Hepatology 46:3, 906-911
CrossRef28
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CrossRef29
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CrossRef30
Zheng, Zhong, Chen, Tingan, Li, Xueli, Haura, Eric, Sharma, Anupama, Bepler, Gerold, . (2007) DNA Synthesis and Repair Genes RRM1 and ERCC1 in Lung Cancer. New England Journal of Medicine 356:8, 800-808
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CrossRef32
F Javier de la Torre, Angel García, Antonio Gil-Moreno, Jesus Planaguma, Jaume Reventos, Santiago Ramón y Cajal, Jordi Xercavins. (2007) Apoptosis in epithelial ovarian tumours. European Journal of Obstetrics & Gynecology and Reproductive Biology 130:1, 121-128
CrossRef33
Denise M. Haynik, Richard A. Prayson. (2006) Immunohistochemical Expression of Bcl-2, Bcl-x, and Bax in Follicular Carcinomas of the Thyroid. Applied Immunohistochemistry & Molecular Morphology 14:4, 417-421
CrossRef34
A. Yaren, I. Oztop, A. Kargi, C. Ulukus, A. Onen, A. Sanli, O. Binicier, U. Yilmaz, M. Alakavuklar. (2006) Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis. International Journal of Clinical Practice 60:6, 675-682
CrossRef35
Maria Rosaria Raspollini, Gianni Amunni, Alessandro Villanucci, Francesca Castiglione, Duccio Rossi Degl??Innocenti, Gianna Baroni, Milena Paglierani, Gian Luigi Taddei. (2006) HER-2/neu and bcl-2 in Ovarian Carcinoma. Applied Immunohistochemistry & Molecular Morphology 14:2, 181-186
CrossRef36
Eelco Fokkema, Wim Timens, Elisabeth G.E. de Vries, Steven de Jong, Vaclav Fidler, Coby Meijer, Harry J.M. Groen. (2006) Expression and prognostic implications of apoptosis-related proteins in locally unresectable non-small cell lung cancers. Lung Cancer 52:2, 241-247
CrossRef37
Loucas Georgiou, George Minopoulos, Nikos Lirantzopoulos, Aliki Fiska-Demetriou, Efstratios Maltezos, Efthimios Sivridis. (2006) Angiogenesis and p53 at the Invading Tumor Edge: Prognostic Markers for Colorectal Cancer Beyond Stage. Journal of Surgical Research 131:1, 118-123
CrossRef38
Ryota Tanaka, Tadashi Ishiyama, Teruhito Uchihara, Yukinori Inadome, Tatsuo Iijima, Yukio Morishita, Junko Kano, Tomoyuki Goya, Masayuki Noguchi. (2006) Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma. Cancer 106:3, 648-653
CrossRef39
Kwang Hyun Paik, Yeon Hee Park, Baek-Yeol Ryoo, Sung Hyun Yang, Jae Cheol Lee, Cheol Hyun Kim, Seung Seog Ki, Jung Min Kim, Myung Joon Park, Heui June Ahn, Won Choi, Jin Haeng Chung. (2006) Prognostic Value of Immunohistochemical Staining of p53, bcl-2, and Ki-67 in Small Cell Lung Cancer. Journal of Korean Medical Science 21:1, 35
CrossRef40
Nurdan Kokturk, Pinar Firat, Hadi Akay, Cem Kadilar, Can Ozturk, Faruk Zorlu, Yucel Gungen, Salih Emri. (2005) Prognostic significance of Bax and Fas Ligand in erionite and asbestos induced Turkish malignant pleural mesothelioma. Lung Cancer 50:2, 189-198
CrossRef41
Daisuke Furuya, Naoki Tsuji, Atsuhito Yagihashi, Naoki Watanabe. (2005) Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity. Experimental Cell Research 307:1, 26-40
CrossRef42
Satoru Munakata, Omi Watanabe, Kazutomo Ohashi, Hideo Morino. (2005) Expression of Fas Ligand and bcl-2 in Cervical Carcinoma and Their Prognostic Significance. American Journal of Clinical Pathology 123:6, 879-885
CrossRef43
Michael J. Morris, Carlos Cordon-Cardo, William K. Kelly, Susan F. Slovin, Karen Siedlecki, Kevin P. Regan, Robert S. DiPaola, Mohamed Rafi, Neal Rosen, Howard I. Scher. (2005) Safety and Biologic Activity of Intravenous BCL-2 Antisense Oligonucleotide (G3139) and Taxane Chemotherapy in Patients With Advanced Cancer. Applied Immunohistochemistry & Molecular Morphology 13:1, 6-13
CrossRef44
P. Vielh, J.-P. Spano, J. Grenier, T. Le Chevalier, J.-C. Soria. (2005) Molecular prognostic factors in resectable non-small cell lung cancer. Critical Reviews in Oncology/Hematology 53:3, 193-197
CrossRef45
R.H.J. Breuer, P.E. Postmus, E.F. Smit. (2005) Molecular Pathology of Non-Small-Cell Lung Cancer. Respiration 72:3, 313-330
CrossRef46
Motohiro Esaki, Takayuki Matsumoto, Satoshi Yao, Shotaro Nakamura, Minako Hirahashi, Takashi Yao, Mitsuo Iida. (2005) Immunohistochemical characteristics of duodenal adenomas in familial adenomatous polyposis with special reference to cell kinetics. Human Pathology 36:1, 66-73
CrossRef47
Päivi Siironen, Stig Nordling, Johanna Louhimo, Reijo Haapiainen, Caj Haglund. (2005) Immunohistochemical Expression of Bcl-2, Ki-67, and p21 in Patients with Papillary Thyroid Cancer. Tumor Biology 26:1, 50-56
CrossRef48
Ryungsa Kim, Manabu Emi, Kazuaki Tanabe, Tetsuya Toge. (2004) Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy. Cancer 101:11, 2491-2502
CrossRef49
Genevieve A. Andrews, Sichuan Xi, Rebecca G. Pomerantz, Charles J. Lin, William E. Gooding, Abbey L. Wentzel, Li Wu, David Sidransky, Jennifer Rubin Grandis. (2004) Mutation of p53 in head and neck squamous cell carcinoma correlates with Bcl-2 expression and increased susceptibility to cisplatin-induced apoptosis. Head & Neck 26:10, 870-877
CrossRef50
Jürgen R. Fischer, Harald Lahm. (2004) Validation of molecular and immunological factors with predictive importance in lung cancer. Lung Cancer 45, S151-S161
CrossRef51
Rao N. Saladi, Fiza Singh, Huachen Wei, Mark G. Lebwohl, Robert G. Phelps. (2004) Use of Ber-EP4 protein in recurrent metastatic basal cell carcinoma: a case report and review of the literature. International Journal of Dermatology 43:8, 600-603
CrossRef52
Klaus L. Prenzel, Stephan E. Baldus, Stefan P. M
nig, Daniela Tack, Jan M. Sinning, Christian A. Gutschow, Guido Grass, Paul M. Schneider, Hans P. Dienes, Arnulf H. H
CrossRef53
Leos Kren, Jan Brazdil, Marketa Hermanova, Viktor N. Goncharuk, Bhaskar V. S. Kallakury, Prabhjot Kaur, Jeffrey S. Ross. (2004) Prognostic Significance of Anti-apoptosis Proteins Survivin and bcl-2 in Non-small Cell Lung Carcinomas. Applied Immunohistochemistry & Molecular Morphology44-49
CrossRef54
Alan D.L Sihoe, Anthony P.C Yim. (2004) Lung cancer staging. Journal of Surgical Research 117:1, 92-106
CrossRef55
Klaus Bodner, Barbara Bodner-Adler, Oliver Kimberger, Klaus Czerwenka, Klaus Mayerhofer. (2004) Bcl-2 expression and other clinicopathologic parameters in uterine leiomyosarcoma. Wiener Klinische Wochenschrift 116:4, 135-139
CrossRef56
Gianfranco Buccheri, Domenico Ferrigno. (2004) Prognostic factors. Hematology/Oncology Clinics of North America 18:1, 187-201
CrossRef57
A M Groeger, V Esposito, A De Luca, R Cassandro, G Tonini, V Ambrogi, F Baldi, R Goldfarb, T C Mineo, A Baldi, E Wolner. (2004) Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small-cell lung cancers. Histopathology 44:1, 54-63
CrossRef58
Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Chang Suk Kang. (2004) The Expression of c-myc, bcl-2 and p53 Proteins in Adenocarcinomas of Lung. Cancer Research and Treatment 36:2, 146
CrossRef59
EF Gaffney. (2004) Apoptosis in cancer: Archaeology, functional relevance and exploitation in novel treatment strategies. Irish Journal of Medical Science 173:1, 40-47
CrossRef60
Kuniaki Nakanishi, Toshiaki Kawai, Fumiyuki Kumaki, Sadayuki Hiroi, Makio Mukai, Eiji Ikeda. (2003) Survivin Expression in Atypical Adenomatous Hyperplasia of the Lung. American Journal of Clinical Pathology 120:5, 712-719
CrossRef61
Jean-Charles Soria, Edward S Kim, Jéôme Fayette, Sylvie Lantuejoul, Eric Deutsch, Waun Ki Hong. (2003) Chemoprevention of lung cancer. The Lancet Oncology 4:11, 659-669
CrossRef62
M Tomita, Y Matsuzaki, M Edagawa, T Shimizu, M Hara, T Onitsuka. (2003) Prognostic significance of bcl-2 expression in resected pN2 non-small cell lung cancer. European Journal of Surgical Oncology (EJSO) 29:8, 654-657
CrossRef63
Jonathan C. Daniel, W. Roy Smythe. (2003) Gene therapy of lung cancer. Seminars in Surgical Oncology 21:3, 196-204
CrossRef64
K Kontogianni, M Demonakou, N Kavantzas, A.Ch Lazaris, K Lariou, C Vourlakou, P Davaris. (2003) Prognostic predictors of gastrointestinal stromal tumors: a multi-institutional analysis of 102 patients with definition of a prognostic index. European Journal of Surgical Oncology (EJSO) 29:6, 548-556
CrossRef65
Bálint Tombor, Kathleen Rundell, Zoltán N Oltvai. (2003) Bcl-2 promotes premature senescence induced by oncogenic Ras. Biochemical and Biophysical Research Communications 303:3, 800-807
CrossRef66
Klaus Bodner, Barbara Bodner-Adler, Klaus Czerwenka, Gernot Hudelist, Oliver Kimberger, Sepp Leodolter, Klaus Mayerhofer. (2003) Bcl-2 expression in a primary leiomyosarcoma of the ovary: A case report. Wiener Klinische Wochenschrift 115:5-6, 191-195
CrossRef67
A. A. Raouf, D. A. Evoy, E. Carton, E. Mulligan, M. M. Griffin, J. V. Reynolds. (2003) Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation. Diseases of the Esophagus 16:1, 17-23
CrossRef68
Vanesa Gregorc, Vienna Ludovini, Lorenza Pistola, Samir Darwish, Irene Floriani, Guido Bellezza, Angelo Sidoni, Antonio Cavaliere, Massimo Scheibel, Verena De Angelis, Emilio Bucciarelli, Maurizio Tonato. (2003) Relevance of p53, bcl-2 and Rb expression on resistance to cisplatin-based chemotherapy in advanced non-small cell lung cancer. Lung Cancer 39:1, 41-48
CrossRef69
P Iyengar. (2002) Clinical relevance of molecular markers in lung cancer. Surgical Oncology 11:4, 167-179
CrossRef70
V Rigau, T.J Molina, C Chaffaud, G Huchon, J Audouin, S Chevret, J.M Bréchot. (2002) Blood vessel invasion in resected non small cell lung carcinomas is predictive of metastatic occurrence. Lung Cancer 38:2, 169-176
CrossRef71
A.B. Schiller, W.S. Clark, G. Cotsonis, D. Lawson, P.B. DeRose, C. Cohen. (2002) Image cytometric bcl-2:bax and bcl-2:bcl-x ratios in invasive breast carcinoma: Correlation with prognosis. Cytometry 50:4, 203-209
CrossRef72
Yih-Leong Chang, Chen-Tu Wu, Jin-Yuan Shih, Yung-Chie Lee. (2002) New Aspects in Clinicopathologic and Oncogene Studies of 23 Pulmonary Lymphoepithelioma-Like Carcinomas. The American Journal of Surgical Pathology 26:6, 715-723
CrossRef73
Christine L Lau, Mary-Beth H Moore, Kelly R Brooks, Thomas A D'Amico, David H Harpole. (2002) Molecular staging of lung and esophageal cancer. Surgical Clinics of North America 82:3, 497-523
CrossRef74
Jürgen Mattern, Reet Koomägi, Manfred Volm. (2002) Characteristics of long-term survivors of untreated lung cancer. Lung Cancer 36:3, 277-282
CrossRef75
Kazushi Shigemasa, Osamu Katoh, Yuko Shiroyama, Shoji Mihara, Keiji Mukai, Nobutaka Nagai, Koso Ohama. (2002) Increased MCL-1 Expression Is Associated with Poor Prognosis in Ovarian Carcinomas. Cancer Science 93:5, 542-550
CrossRef76
Tomoyuki Dan'ura, Akira Kawai, Yuki Morimoto, Noriko Naito, Aki Yoshida, Hajime Inoue. (2002) Apoptosis and expression of its regulatory proteins in soft tissue sarcomas. Cancer Letters 178:2, 167-174
CrossRef77
Douglas K. Trask, Gregory T. Wolf, Carol R. Bradford, Susan G. Fisher, Kenneth Devaney, Mark Johnson, Timothy Singleton, Max Wicha. (2002) Expression of Bcl-2 Family Proteins in Advanced Laryngeal Squamous Cell Carcinoma: Correlation With Response to Chemotherapy and Organ Preservation. The Laryngoscope 112:4, 638-644
CrossRef78
Kwun M Fong, John D Minna. (2002) Molecular biology of lung cancer: Clinical implications. Clinics in Chest Medicine 23:1, 83-101
CrossRef79
Sabine Zöchbauer-Müller, Adi F. Gazdar, John D. Minna. (2002) M
OLECULAR PATHOGENESIS OF LUNG CANCER . Annual Review of Physiology 64:1, 681-708
CrossRef80
Patrick P Koty, Haifan Zhang, Wilbur A Franklin, Samuel A Yousem, Rodney Landreneau, Mark L Levitt. (2002) In vivo expression of p53 and Bcl-2 and their role in programmed cell death in premalignant and malignant lung lesions. Lung Cancer 35:2, 155-163
CrossRef81
Giles Cox, J Louise Jones, Allan Andi, Keith R Abrams, Kenneth J O'Byrne. (2001) Bcl-2 is an independent prognostic factor and adds to a biological model for predicting outcome in operable non-small cell lung cancer. Lung Cancer 34:3, 417-426
CrossRef82
Atsuhisa Tamura, Akira Hebisawa, Koji Hayashi, Yuzo Sagara, Kanae Fukushima, Atsuyuki Kurashima, Hideki Yotsumoto, Masashi Mori, Hikotaro Komatsu. (2001) Prognostic significance of thrombomodulin expression and vascular invasion in stage I squamous cell carcinoma of the lung. Lung Cancer 34:3, 375-382
CrossRef83
Chrisoula Scopa, Constantine Vagianos, Dimitrios Kardamakis, Theodore Kourelis, Haralabos Kalofonos, Athanassios Tsamandas. (2001) Applied Immunohistochemistry 9:4, 329-334
CrossRef84
Frederic J Kaye. (2001) Molecular biology of lung cancer. Lung Cancer 34, S35-S41
CrossRef85
Kenzo Hiroshima, Tetsuya Toyozaki, Akira Iyoda, Toshikazu Yusa, Takehiko Fujisawa, Hidemi Ohwada. (2001) Apoptosis and proliferative activity in mature and immature teratomas of the mediastinum. Cancer 92:7, 1798-1806
CrossRef86
Mikhail V. Blagosklonny. (2001) Paradox of Bcl-2 (and p53): why may apoptosis-regulating proteins be irrelevant to cell death?. BioEssays 23:10, 947-953
CrossRef87
Tomoyoshi Takayama, Mitsuo Nagao, Hidetomo Sawada, Yukishige Yamada, Kouji Emoto, Heisuke Fujimoto, Masato Ueno, Shuya Hirao, Yoshiyuki Nakajima. (2001) Bcl-X expression in esophageal squamous cell carcinoma: Association with tumor progression and prognosis. Journal of Surgical Oncology 78:2, 116-123
CrossRef88
Sarkis H. Meterissian, Maria Kontogiannea, Mohamed Al-Sowaidi, Ayman Linjawi, Fawaz Halwani, Bruce Jamison, Michael Edwardes. (2001) Bcl-2 Is a Useful Prognostic Marker in Dukes? B Colon Cancer. Annals of Surgical Oncology 8:6, 533-537
CrossRef89
Nam Kyu Kim, Jae Kun Park, Kang Yong Lee, Woo IK Yang, Seong Hyeon Yun, JinSil Sung, Jin Sik Min. (2001) p53, BCL-2, and Ki-67 Expression According to Tumor Response After Concurrent Chemoradiotherapy for Advanced Rectal Cancer. Annals of Surgical Oncology 8:5, 418-424
CrossRef90
A HOMMA, Y FURUTA, N ORIDATE, Y NAKANO, K YAGI, T NAGAHASHI, S FUKUDA, Y INUYAMA. (2001) Correlation of clinicopathological parameters and biological markers related to apoptosis and proliferative activity with a clinical outcome in squamous cell carcinoma of the larynx treated with concurrent chemoradiotherapy. Auris Nasus Larynx 28, S87-S94
CrossRef91
Georgios Papakonstantinou, Caroline Verbeke, Jan Hastka, Manfred Bohrer, Rudiger Hehlmann. (2001) bcl-2 expression in non-Hodgkin's lymphomas is not associated with bcl-2 gene rearrangements. British Journal of Haematology 113:2, 383-390
CrossRef92
Yoshinori Nio, Chikage Iguchi, Kunihiro Yamasawa, Susumu Sasaki, Michio Takamura, Tomoko Toga, Ming Dong, Masayuki Itakura, Katsuhiro Tamura. (2001) Apoptosis and Expression of Bcl-2 and Bax Proteins in Invasive Ductal Carcinoma of the Pancreas. Pancreas 22:3, 230-239
CrossRef93
Laurent L. Ozbun, Liang You, Sharon Kiang, Jerry Angdisen, Alfredo Martinez, Sonia B. Jakowlew. (2001) Identification of Differentially Expressed Nucleolar TGF-β1 Target (DENTT) in Human Lung Cancer Cells That Is a New Member of the TSPY/SET/NAP-1 Superfamily. Genomics 73:2, 179-193
CrossRef94
O. Gautschi, S. Tschopp, R. A. Olie, S. H. Leech, A. P. Simoes-Wust, A. Ziegler, B. Baumann, B. Odermatt, J. Hall, R. A. Stahel, U. Zangemeister-Wittke. (2001) Activity of a Novel bcl-2/bcl-xL-Bispecific Antisense Oligonucleotide Against Tumors of Diverse Histologic Origins. JNCI Journal of the National Cancer Institute 93:6, 463-471
CrossRef95
Eva Forgacs, Sabine Zöchbauer-Müller, Edit Oláh, John D. Minna. (2001) Molecular genetic abnormalities in the pathogenesis of human lung cancer. Pathology & Oncology Research 7:1, 6-13
CrossRef96
Yoshinori Nio, Ming Dong, Chikage Iguchi, Kunihiro Yamasawa, Tomoko Toga, Masayuki Itakura, Katsuhiro Tamura. (2001) Expression of Bcl-2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: Effects on clinical outcome and efficacy of adjuvant chemotherapy. Journal of Surgical Oncology 76:3, 188-196
CrossRef97
Harri Vainio. (2001) Review Use of biomarkers in risk assessment. International Journal of Hygiene and Environmental Health 204:2-3, 91-102
CrossRef98
Sopaporn Niemhom, Sohei Kitazawa, Shinichi Murao, Somyos Kunachak, Sakan Maeda. (2000) Co-expression of p53 and bcl-2 may correlate to the presence of Epstein–Barr virus genome and the expression of proliferating cell nuclear antigen in nasopharyngeal carcinoma. Cancer Letters 160:2, 199-208
CrossRef99
Mitsutoshi Shiba, Hiromasa Kohno, Kimitaka Kakizawa, Toshihiko Iizasa, Mizuto Otsuji, Yukio Saitoh, Kenzo Hiroshima, Hidemi Ohwada, Takehiko Fujisawa. (2000) Ki-67 immunostaining and other prognostic factors including tobacco smoking in patients with resected nonsmall cell lung carcinoma. Cancer 89:7, 1457-1465
CrossRef100
Hong-Fang Yin, Norihiko Okada, Minoru Takagi. (2000) Apoptosis and apoptotic-related factors in mucoepidermoid carcinoma of the oral minor salivary glands. Pathology International 50:8, 603-609
CrossRef101
Cecilia Bozzetti, Vittorio Franciosi, Pellegrino Crafa, Paolo Carbognani, Michele Rusca, Rita Nizzoli, Annamaria Guazzi, Nadia Naldi, Giorgio Cocconi. (2000) Biological variables in non-small cell lung cancer: comparison between immunocytochemical determination on fine needle aspirates from surgical specimens and immunohistochemical determination on tissue sections. Lung Cancer 29:1, 33-41
CrossRef102
Caroline M. Abramovich, Richard A. Prayson. (2000) Apoptotic Activity and bcl-2 Immunoreactivity in Meningiomas: Association With Grade and Outcome. American Journal of Clinical Pathology 114:1, 84-92
CrossRef103
Alexandre de la Taille, Ralph Buttyan, Aaron E Katz, James McKiernan, Martin Burchardt, Tatjana Burchardt, Dominique K Chopin, Ihor S Sawczuk. (2000) Biomarkers of renal cell carcinoma. Urologic Oncology: Seminars and Original Investigations 5:4, 139-148
CrossRef104
G. Ferrandina, S. Mozzetti, M. Marone, A. Fagotti, G. Macchia, S. Mancuso, G. Scambia. (2000) Bcl-2, bax, bcl-xL and bcl-xS expression in neoplastic and normal cervical tissue. Cancer Letters 155:1, 19-27
CrossRef105
Giles Cox, Rosemary A. Walker, Salli Muller, Keith R. Abrams, William P. Steward, Kenneth Jo’byrne. (2000) Does immunointensity account for the differences in prognostic significance of Bcl-2 expression in non-small cell lung cancer?. Pathology & Oncology Research 6:2, 87-92
CrossRef106
Lucio Cagini, Massimo Monacelli, Giammario Giustozzi, Luigi Moggi, Guido Bellezza, Angelo Sidoni, Emilio Bucciarelli, Samir Darwish, Vienna Ludovini, Lorenza Pistola, Vanesa Gregorc, Maurizio Tonato. (2000) Biological prognostic factors for early stage completely resected non-small cell lung cancer. Journal of Surgical Oncology 74:1, 53-60
CrossRef107
S Munakata, T Enomoto, M Tsujimoto, Y Otsuki, H Miwa, H Kanno, V Langrish. (2000) Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms. British Journal of Cancer 82:8, 1446-1452
CrossRef108
George L. Zorn, Jonathan C. Nesbitt. (2000) Surgical management of early stage lung cancer. Seminars in Surgical Oncology 18:2, 124-136
CrossRef109
Inge Tinhofer, PhD, Ingrid Marschitz, MD, Marion Kos, Richard Greil, MD, Anton Hittmair, MD, Alexander Egle, MD. (2000) Analysis of Bcl-2 Protein Expression in Chronic Lymphocytic Leukemia. American Journal of Clinical Pathology 113:2, 219-229
CrossRef110
Wood-Yee Chan, Kwok-Kuen Cheung, John O. Schorge, Lee-Wen Huang, William R. Welch, Debra A. Bell, Ross S. Berkowitz, Samuel C. Mok. (2000) Bcl-2 and p53 Protein Expression, Apoptosis, and p53 Mutation in Human Epithelial Ovarian Cancers. The American Journal of Pathology 156:2, 409-417
CrossRef111
Keiichi Saito, Shiro Mori, Naoko Tanda, Seizaburo Sakamoto. (2000) Immunolocalization of c-Myc and bcl-2 Proto-Oncogene Products in Gingival Hyperplasia Induced by Nifedipine and Phenytoin. Journal of Periodontology 71:1, 44-49
CrossRef112
Michael E. Gruidl, Gail L. Shaw Wright. (2000) Potential Biomarkers for the Early Detection of Lung Cancer. Journal of Thoracic Imaging 15:1, 13-20
CrossRef113
Michael I. Koukourakis, Alexandra Giatromanolaki, Francesca Guddo, Loukas Kaklamanis, Maurizio Vignola, Stelios Kakolyris, Hellen Turley, Vassilios Georgoulias, Giovanni Bonsignore, Kevin C. Gatter, Adrian L. Harris. (2000) c-erbB-2 and Episialin Challenge Host Immune Response by HLA Class I Expression in Human Non???Small-Cell Lung Cancer. Journal of Immunotherapy 23:1, 104-114
CrossRef114
Kwun M. Fong, Yoshitaka Sekido, John D. Minna. (1999) Molecular pathogenesis of lung cancer. The Journal of Thoracic and Cardiovascular Surgery 118:6, 1136-1152
CrossRef115
Monimoy Ghosh, John Crocker, Alan G. Morris. (1999) CD40 and Bcl2 expression in squamous cell carcinoma of the lung: correlation with apoptosis, survival, and other clinicopathological factors. The Journal of Pathology 189:3, 363-367
CrossRef116
Alexandra Giatromanolaki, George P. Stathopoulos, Eleni Tsiobanou, Costandina Papadimitriou, Vassilios Georgoulias, Kevin C. Gatter, Adrian L. Harris, Michael I. Koukourakis. (1999) Combined role of tumor angiogenesis,bcl-2, and p53 expression in the prognosis of patients with colorectal carcinoma. Cancer 86:8, 1421-1430
CrossRef117
Leahy, Mulcahy, O'Donoghue, Parfrey. (1999) bcl-2 protein expression is associated with better prognosis in colorectal cancer. Histopathology 35:4, 360-367
CrossRef118
Cheng-long Huang, Nobuoki Kohno, Haruhiko Inufusa, Ken Kodama, Toshihiko Taki, Masayuki Miyake. (1999) Overexpression of bax Associated with Mutations in the Loop-Sheet-Helix Motif of p53. The American Journal of Pathology 155:3, 955-965
CrossRef119
Anna-Kaisa Eerola, Henni Ruokolainen, Ylermi Soini, Hannu Raunio, Paavo PÄÄKKÖ. (1999) Accelerated apoptosis and low Bcl-2 expression associated with neuroendocrine differentiation predict shortened survival in operated large cell carcinoma of the lung. Pathology & Oncology Research 5:3, 179-186
CrossRef120
Josef Müller-Höcker. (1999) Immunoreactivity of p53, Ki-67, and Bcl-2 in oncocytic adenomas and carcinomas of the thyroid gland. Human Pathology 30:8, 926-933
CrossRef121
Tomasz Kr̨ecicki, Michal Jelén, Maria Zalesska-Kr̨e cicka, Teresa Szkudlarek, Krzysztof Szajowski. (1999) Immunohistochemically stained markers (p53, PCNA, bcl-2) in dysplastic lesions of the larynx. Cancer Letters 143:1, 23-28
CrossRef122
Hidemi Izawa, Nobuhisa Yonemitsu, Takemoto Shin, Hajime Sugihara. (1999) Histopathological analysis of apoptosis, and expression of p53, bcl-2, bax, and Ki-67 in laryngeal squamous cell carcinomas and dysplasia. Auris Nasus Larynx 26:3, 317-330
CrossRef123
Anirban Maitra, Robin H Amirkhan, M.Hossein Saboorian, William H Frawley, Raheela Ashfaq. (1999) Survival in small cell lung carcinoma is independent of Bcl-2 expression. Human Pathology 30:6, 712-717
CrossRef124
Thomas A. D'Amico, MD, Marga Massey, MD, James E. Herndon II, PhD, Mary-Beth Moore, David H. Harpole. (1999) A biologic risk model for stage I lung cancer: Immunohistochemical analysis of 408 patients with the use of ten molecular markers. The Journal of Thoracic and Cardiovascular Surgery 117:4, 736-743
CrossRef125
Wendy L. Heusch, Rhoda Maneckjee. (1999) Effects of bombesin on methadone-induced apoptosis of human lung cancer cells. Cancer Letters 136:2, 177-185
CrossRef126
Patrick P. Koty, Haifan Zhang, Mark L. Levitt. (1999) Antisense bcl-2 treatment increases programmed cell death in non-small cell lung cancer cell lines. Lung Cancer 23:2, 115-127
CrossRef127
Jozsef Piffko, Agnes Bankfalvi, Ulrich Joos, Dietmar Ofner, Melanie Krassort, Kurt Werner Schmid. (1999) Immunophenotypic Analysis of Normal Mucosa and Squamous Cell Carcinoma of the Oral Cavity. Cancer Detection <html_ent glyph="@amp;" ascii="&"/> Prevention 23:1, 45-56
CrossRef128
Alfredo Santinelli, Renzo Ranaldi, Mariagrazia Baccarini, Bruno Mannella, Italo Bearzi. (1999) Ploidy, Proliferative Activity, p53 and bcl-2 Expression in Bronchopulmonary Carcinoids: Relationship with Prognosis. Pathology - Research and Practice 195:7, 467-474
CrossRef129
John C. Pena, Craig B. Thompson, Wendy Recant, Everett E. Vokes, Charles M. Rudin. (1999) Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck. Cancer 85:1, 164-170
CrossRef130
Anne E Willis. (1999) Translational control of growth factor and proto-oncogene expression. The International Journal of Biochemistry & Cell Biology 31:1, 73-86
CrossRef131
L. Nakopoulou, K. Stefanaki, Ch. Vourlakou, N. Manolaki, H. Gakiopoulou, G. Michalopoulos. (1999) Bcl-2 protein expression in acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma. Pathology - Research and Practice 195:1, 19-24
CrossRef132
Young-Chul Kim, Kyung-Ok Park, Jeffrey A. Kern, Chang-Soo Park, Sung-Chul Lim, An-Soo Jang, Jae-Beom Yang. (1998) The interactive effect of Ras, HER2, P53 and Bcl-2 expression in predicting the survival of non-small cell lung cancer patients. Lung Cancer 22:3, 181-190
CrossRef133
Harri Vainio. (1998) Use of biomarkers — new frontiers in occupational toxicology and epidemiology. Toxicology Letters 102-103, 581-589
CrossRef134
Pauline Athanassiadou, Theodosios Dosios, Efthalia Petrakakou, Anna Liossi, Cherry Zerva, Peter Athanassiades. (1998) p53 and bcl-2 protein expression in non-small-cell lung carcinoma. Diagnostic Cytopathology 19:4, 255-259
CrossRef135
R. Dziadziuszko, E. Jassem, J. Jassem. (1998) Clinical implications of molecular abnormalities in lung cancer. Cancer Treatment Reviews 24:5, 317-330
CrossRef136
Muneyuki Masuda, Atushi Shinokuma, Naoya Hirakawa, Torahiko Nakashima, Sohtaro Komiyama. (1998) Expression of bcl-2-, p53, and Ki-67 and outcome of patients with primary nasopharyngeal carcinomas following DNA-damaging treatment. Head & Neck 20:7, 640-644
CrossRef137
Florin Sirzén, Boris Zhivotovsky, Anders Nilsson, Jonas Bergh, Rolf Lewensohn. (1998) Higher spontaneous apoptotic index in small cell compared with non-small cell lung carcinoma cell lines; lack of correlation with Bcl-2/Bax. Lung Cancer 22:1, 1-13
CrossRef138
Y. Soini, P. Pääkkö, V-P. Lehto. (1998) Histopathological Evaluation of Apoptosis in Cancer. The American Journal of Pathology 153:4, 1041-1053
CrossRef139
J.Rebecca Liu, Bridget Fletcher, Carmen Page, Changzhi Hu, Gabriel Nunez, Vicki Baker. (1998) Bcl-xLIs Expressed in Ovarian Carcinoma and Modulates Chemotherapy-Induced Apoptosis. Gynecologic Oncology 70:3, 398-403
CrossRef140
Yoshitaka Sekido, Kwun M. Fong, John D. Minna. (1998) Progress in understanding the molecular pathogenesis of human lung cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1378:1, F21-F59
CrossRef141
Hanna Eid, Miklos Guly
CrossRef142
Ter Harmsel, van Muyden, Smedts, Hermans, Kuijpers, Raikhlin, Petrov, Lebedev, Ramaekers, Trimbos. (1998) The significance of cell type and tumor growth markers in the prognosis of unscreened cervical cancer patients. International Journal of Gynecological Cancer 8:4, 336-344
CrossRef143
Tatsuya Ohno, Takashi Nakano, Yuzuru Niibe, Hirohiko Tsujii, Kuniyuki Oka. (1998) Bax protein expression correlates with radiation-induced apoptosis in radiation therapy for cervical carcinoma. Cancer 83:1, 103-110
CrossRef144
Saul Suster, Cyril Fisher, Cesar A. Moran. (1998) Expression of bcl-2 Oncoprotein in Benign and Malignant Spindle Cell Tumors of Soft Tissue, Skin, Serosal Surfaces, and Gastrointestinal Tract. The American Journal of Surgical Pathology 22:7, 863-872
CrossRef145
Fen-Fen Chen, Jing-Jou Yan, Wu-Wei Lai, Ying-Tai Jin, Ih-Jen Su. (1998) Epstein-barr virus-associated nonsmall cell lung carcinoma. Cancer 82:12, 2334-2342
CrossRef146
M. Reěl, I. Friedmann, J. Šimek, V. Chrobok, J. Bukač, L. Plíšková. (1998) Pulmonary paraganglioid carcinoids and bcl-2 oncoprotein expression. Endocrine Pathology 9:2, 149-155
CrossRef147
Christophe Guichard, Laurent Gilain, Issam Abd Al Samad, Gaëlle Piron, Lydia Brugel, Estelle Escudier, André Coste. (1998) Epithelial Cell Proliferation, Apoptosis, and Apoptosis Inhibition in Inverted Papillomas. The Laryngoscope 108:5, 716-720
CrossRef148
John Nemunaitis, Steven Klemow, Alex Tong, Alice Courtney, Walter Johnston, Michael Mack, Wayne Taylor, Max Solano, Marvin Stone, John Mallams, Gabriele Mues. (1998) Prognostic Value of K-ras Mutations, ras Oncoprotein, and c-erb B-2 Oncoprotein Expression in Adenocarcinoma of the Lung. American Journal of Clinical Oncology 21:2, 155-160
CrossRef149
EDWARD J. KIRSH, DAVID A. BAUNOCH, WALTER M. STADLER. (1998) EXPRESSION OF BCL-2 AND BCL-X IN BLADDER CANCER. The Journal of Urology 159:4, 1348-1353
CrossRef150
Vesna Čemerikić-Martinović, Dušan Trpinac, Maja Ercegovac. (1998) Correlations between mitotic and apoptotic indices, number of interphase NORs, and histological grading in squamous cell lung cancer. Microscopy Research and Technique 40:5, 408-417
CrossRef151
Da-Gong Wang, Colin F. Johnston, James M. Sloan, Keith D. Buchanan. (1998) Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53. The Journal of Pathology 184:3, 247-251
CrossRef152
P.A. Ellis, I.E. Smith, S. Detre, S.A. Burton, J. Salter, R. A'Hern, G. Walsh, S.R.D. Johnston, M. Dowsett. (1998) Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy. Breast Cancer Research and Treatment 48:2, 107-116
CrossRef153
M. Katabami, H. Dosaka-Akita, K. Honma, K. Kimura, M. Fujino, Y. Uchida, H. Mikami, Y. Ohsaki, Y. Kawakami, K. Kikuchi. (1998) p53 and Bcl-2 expression in pneumoconiosis-related pre-cancerous lesions and lung cancers: Frequent and preferential p53 expression in pneumoconiotic bronchiolar dysplasias. International Journal of Cancer 75:4, 504-511
CrossRef154
Lydia Nakopoulou, Christina Vourlakou, Anastasios Zervas, Anastasia Tzonou, Hariklia Gakiopoulou, Meletios-Athanasios Dimopoulos. (1998) The prevalence of bcl-2, p53, and ki-67 immunoreactivity in transitional cell bladder carcinomas and their clinicopathologic correlates. Human Pathology 29:2, 146-154
CrossRef155
Eva Karamitopoulou, Elias Perentes, Markus Tolnay, Alphonse Probst. (1998) Prognostic significance of MIB-1, p53, and bcl-2 immunoreactivity in meningiomas. Human Pathology 29:2, 140-145
CrossRef156
Wiebren Tjalma, Eva De Cuyper, Joost Weyler, Eric Van Marck, Christel De Pooter, Georges Albertyn, Peter van Dam. (1998) Expression of bcl-2 in invasive and in situ carcinoma of the uterine cervix. American Journal of Obstetrics and Gynecology 178:1, 113-117
CrossRef157
Moore, Ohene-Fianko, Garcia, Chakrabarti. (1998) Apoptosis in thyroid neoplasms: relationship with p53 and bcl-2 expression. Histopathology 32:1, 35-42
CrossRef158
M.V Fleming, D.G Guinee, W.S Chu, A.N Freedman, N.E Caporaso, W.P Bennett, T.V Colby, H Tazelaar, S.L Abbondanzo, J Jett, P Pairolero, V Trastek, L.A Liotta, C.C Harris, W.D Travis. (1998) Bcl-2 immunohistochemistry in a surgical series of non-small cell lung cancer patients. Human Pathology 29:1, 60-64
CrossRef159
Michael I. Koukourakis, Alexandra Giatromanolaki, Kenneth J. O'Byrne, Ruth M. Whitehouse, Denis C. Talbot, Kevin C. Gatter, Adrian L. Harris. (1997) Potential role ofbcl-2 as a suppressor of tumour angiogenesis in non-small-cell lung cancer. International Journal of Cancer 74:6, 565-570
CrossRef160
Alfonso Due
CrossRef161
Shigeto Kawauchi, Shin-ichi Noguchi, Toshiro Fukuda, Masazumi Tsuneyoshi. (1997) Subcellular localization of Bcl-2 protein in synovial sarcoma. Pathology International 47:12, 854-861
CrossRef162
Mario Sarbia, Fernando Bittinger, Florian Grabellus, Patrick Verreet, Philipp Dutkowski, Rainhart Willers, Helmut E. Gabbert. (1997) Expression of Bax, a pro-apoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma. International Journal of Cancer 73:4, 508-513
CrossRef163
S. Veneroni, R. Silvestrini, A. Costa, P. Salvatori, A. Faranda, R. Molinari. (1997) Biological indicators of survival in patients treated by surgery for squamous cell carcinoma of the oral cavity and oropharynx. Oral Oncology 33:6, 408-413
CrossRef164
Lodovico Balducci, Martine Extermann. (1997) Cancer chemotherapy in the older patient. Cancer 80:7, 1317-1322
CrossRef165
Juan P Palazzo, Nicole J Kafka, Luigi Grasso, Fatima Chakrani, Cheryl Hanau, Kimberly H Cuesta, W.Edward Mercer. (1997) The role of p53, p21WAF1/C1P1, and bcl-2 in radioresistant colorectal carcinoma. Human Pathology 28:10, 1189-1195
CrossRef166
Iwao Nakazato, Tsuneo Hirayasu, Yoshihiko Kamada, Kyoko Tsuhako, Teruo Iwamasa. (1997) Carcinoma of the lung in Okinawa, Japan: With special reference to squamous cell carcinoma and squamous metaplasia. Pathology International 47:10, 659-672
CrossRef167
Gaëlle Ferrières, Marguerite Cuny, Joëlle Simony-Lafontaine, Jocelyne Jacquemier, Caroline Rouleau, Françoise Guilleux, Jean Grenier, Philippe Rouanet, Henri Pujol, Philippe Jeanteur, Chantal Escot. (1997) Variation of bcl-2 expression in breast ducts and lobules in relation to plasma progesterone levels: overexpression and absence of variation in fibroadenomas. The Journal of Pathology 183:2, 204-211
CrossRef168
Shin-Ichi Noguchi, Takashi Ueki, Shigeto Kawauchi, Toshiro Fukuda, Hiroshi Matsuura, Takashi Sonoda, Masazumi Tsuneyoshi. (1997) Establishment and characterization of a new synovial sarcoma cell line, SN-SY-1: Special reference to bcl-2 protein and SYT-SSX1 hybrid transcripts. International Journal of Cancer 72:6, 995-1002
CrossRef169
Hironori Ishida, Koji Irie, Tsuyoshi Itoh, Tsugio Furukawa, Osamu Tokunaga. (1997) The prognostic significance of p53 andbcl-2 expression in lung adenocarcinoma and its correlation with ki-67 growth fraction. Cancer 80:6, 1034-1045
CrossRef170
Fumio Yamasaki, Osamu Tokunaga, Hajime Sugimori. (1997) Apoptotic Index in Ovarian Carcinoma: Correlation with Clinicopathologic Factors and Prognosis. Gynecologic Oncology 66:3, 439-448
CrossRef171
Carol S. Trempus, Joseph K. Haseman, Raymond W. Tennant. (1997) Decreases in phorbol ester–induced papilloma development in v-Ha-ras transgenic TG.AC mice during reduced gene dosage ofbcl-2. Molecular Carcinogenesis 20:1, 68-77
CrossRef172
Rose C Anton, Richard W Brown, Mamoun Younes, Margaret M Gondo, Mark A Stephenson, Philip T Cagle. (1997) Absence of prognostic significance of bcl-2 immunopositivity in non-small cell lung cancer: Analysis of 427 cases. Human Pathology 28:9, 1079-1082
CrossRef173
Naohiko Koide, Shoichiro Koike, Wataru Adachi, Jun Amano, Nobuteru Usuda, Tetsuji Nagata. (1997) Immunohistochemical expression of bcl-2 protein in squamous cell carcinoma and basaloid carcinoma of the esophagus. Surgery Today 27:8, 685-691
CrossRef174
Makoto Saegusa, Isao Okayasu. (1997) Bcl-2 is closely correlated with favorable prognostic factors and inversely associated with p53 protein accumulation in endometrial carcinomas: immunohistochemical and polymerase chain reaction/loss of heterozygosity findings. Journal of Cancer Research and Clinical Oncology 123:8, 429-434
CrossRef175
P. Vermylen, C. Roufosse, V. Ninane, J-P. Sculier. (1997) Biology of pulmonary preneoplastic lesions. Cancer Treatment Reviews 23:4, 241-262
CrossRef176
Gajja S. Salomons, Hugh J.M. Brady, Manon Verwijs-Janssen, Joop D. Van Den Berg, Augustinus A.M. Hart, Henk Van Den Berg, Henk Behrendt, Karel Hahlen, Lou A. Smets. (1997) The Baxα:Bcl-2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia. International Journal of Cancer 71:6, 959-965
CrossRef177
Stephen L. Graziano. (1997) Non-small cell lung cancer: clinical value of new biological predictors. Lung Cancer 17, S37-S58
CrossRef178
Takao Inada, Akira Ichikawa, Seiji Igarashi, Tetsuro Kubota, Yoshiro Ogata. (1997) Effect of preoperative 5-fluorouracil on apoptosis of advanced gastric cancer. Journal of Surgical Oncology 65:2, 106-110
CrossRef179
H.Aydanur Kargi, Safiye Aktaş, Özgül Sağol, Sülün Ermete, Oya Akpinar, Atilla Akkoçlu. (1997) Apoptosis bcl-2 and p53 expression and their relation to tumour stage in non-small cell lung carcinomas (NSCLC). Cancer Letters 116:2, 185-189
CrossRef180
Gary M. Strauss. (1997) PROGNOSTIC MARKERS IN RESECTABLE NON–SMALL CELL LUNG CANCER. Hematology/Oncology Clinics of North America 11:3, 409-434
CrossRef181
Makoto Ohbu, Makoto Saegusa, Nobuyuki Kobayashi, Hideto Tsukamoto, Hironobu Mieno, Akira Kakita, Isao Okayasu. (1997) Expression ofbcl-2 protein in esophageal squamous cell carcinomas and its association with lymph node metastasis. Cancer 79:7, 1287-1293
CrossRef182
John McClure. (1997) ADVANCES IN THE UNDERSTANDING OF THE MOLECULAR PATHOLOGY OF CONNECTIVE TISSUE NEOPLASMS. The Journal of Pathology 181:4, 357-358
CrossRef183
MARCO CHILOSI, FABIO FACCHETTI, ANGELO P. DEI TOS, MAURIZIO LESTANI, MARIA L. MORASSI, GUIDO MARTIGNONI, CLAUDIO SORIO, ALICE BENEDETTI, LUCA MORELLI, CLAUDIO DOGLIONI, MASSIMO BARBERIS, FABIO MENESTRINA, GIUSEPPE VIALE. (1997) bcl-2 EXPRESSION IN PLEURAL AND EXTRAPLEURAL SOLITARY FIBROUS TUMOURS. The Journal of Pathology 181:4, 362-367
CrossRef184
Henrik B. Hellquist, Kaarina Sundelin, Alessandra Di Bacco, Macie Tytor, Michela Manzotti, Giuseppe Viale. (1997) Tumour growth fraction and apoptosis in salivary gland acinic cell carcinomas. Prognostic implications of Ki-67 andbcl-2 expression and ofin situ end labelling (TUNEL). The Journal of Pathology 181:3, 323-329
CrossRef185
Toshitsugu Nakamura, Setsuo Nomura, Toshihiko Sakai, Shoji Nariya. (1997) Expression of bcl-2 oncoprotein in gastrointestinal and uterine carcinomas and their premalignant lesions. Human Pathology 28:3, 309-315
CrossRef186
Masahiko Higashiyama, Osamu Doi, Ken Kodama, Hideoki Yokouchi, Shoji Nakamori, Ryuhei Tateishi. (1997) bcl-2 oncoprotein in surgically resected nonsmall cell lung cancer: Possibly favorable prognostic factor in association with low incidence of distant metastasis. Journal of Surgical Oncology 64:1, 48-54
CrossRef187
Luciano Lombardi, Simona Frigerio, Paola Collini, Silvana Pilotti. (1997) Immunocytochemical and Immunoelectron Microscopical Analysis of BCL2 Expression in Thyroid Oxyphilic Tumors. Ultrastructural Pathology 21:1, 33-39
CrossRef188
Nilgun Kapucuoglu, Luisa Losi, Vincenzo Eusebi. (1997) Immunohistochemical localization of Bcl-2 and Bax proteins in in situ and invasive duct breast carcinomas. Virchows Archiv 430:1, 17-22
CrossRef189
Valeria Manetto, Rossana Lorenzini, Carlos Cordon-Cardo, Stan Krajewski, Juan Rosai, John C. Reed, Vincenzo Eusebi. (1997) Bcl-2 and Bax expression in thyroid tumours An immunohistochemical and Western blot analysis. Virchows Archiv 430:2, 125-130
CrossRef190
Mary T. Sheridan, Tadgh O'Dwyer, Colin B. Seymour, Carmel E. Mothersill. (1997) Potential indicators of radiosensitivity in squamous cell carcinoma of the head and neck. Radiation Oncology Investigations 5:4, 180-186
CrossRef191
M. Borges, J.P. Sculier, M. Paesmans, M. Richez, G. Bureau, G. Dabouis, J. Lecomte, J. Michel, O. Van Cutsem, J. Schmerber, V. Giner, M.C. Berchier, R. Sergysels, P. Mommen, J. Klastersky. (1996) Prognostic factors for response to chemotherapy containing platinum derivatives in patients with unresectable non-small cell lung cancer (NSCLC). Lung Cancer 16:1, 21-33
CrossRef192
Bharathy Kumaravel, Koji Arihiro, Mayumi Kaneko, Satoshi Fujii, Kouki Inai. (1996) Expression ofbcl-2 protein in breast carcinoma with correlation to expression ofp53 protein and clinicopathological factors. Breast Cancer 3:3, 173-179
CrossRef193
H.B. Kwa, M.G.M.M. Verheijen, S.V. Litvinov, J.H. Dijkman, W.J. Mooi, J.H.J.M. Van Krieken. (1996) Prognostic factors in resected non-small cell lung cancer: an immunohistochemical study of 39 cases. Lung Cancer 16:1, 35-45
CrossRef194
R.C.K. Jordan, G.C. Catzavelos, A.W. Barrett, P.M. Speight. (1996) Differential expression of bcl-2 and bax in squamous cell carcinomas of the oral cavity. European Journal of Cancer. Part B: Oral Oncology 32:6, 394-400
CrossRef195
MAKOTO SAEGUSA, YOKO KAMATA, MASAKO ISONO, ISAO OKAYASU. (1996) Bcl-2 EXPRESSION IS CORRELATED WITH A LOW APOPTOTIC INDEX AND ASSOCIATED WITH PROGESTERONE RECEPTOR IMMUNOREACTIVITY IN ENDOMETRIAL CARCINOMAS. The Journal of Pathology 180:3, 275-282
CrossRef196
Naoya Hirakawa, Takahiko Naka, Ichiro Yamamoto, Toshiro Fukuda, Masazumi Tsuneyoshi. (1996) Overexpression of bcl-2 protein in synovial sarcoma: A comparative study of other soft tissue spindle cell sarcomas and an additional analysis by fluorescence in situ hybridization. Human Pathology 27:10, 1060-1065
CrossRef197
Mario Sarbia, Fernando Bittinger, Rainer Porschen, Patrick Verreet, Philipp Dutkowski, Reinhart Willers, Helmut E. Gabbert. (1996) bcl-2 expression and prognosis in squamous-cell carcinomas of the esophagus. International Journal of Cancer 69:4, 324-328
CrossRef198
R. Grover, G.D. Wilson. (1996) Bcl-2 expression in malignant melanoma and its prognostic significance. European Journal of Surgical Oncology (EJSO) 22:4, 347-349
CrossRef199
U. Kaiser, M. Schilli, U. Haag, K. Neumann, H. Kreipe, E. Kogan, K. Havemann. (1996) Expression of bcl-2 — protein in small cell lung cancer. Lung Cancer 15:1, 31-40
CrossRef200
Wenliang Wang, Henry Johansson, Tomas Kvasnicka, Lars-Ove Farnebo, Lars Grimelius. (1996) Detection of apoptotic cells and expression of Ki-67 antigen, Bcl-2, p 53 oncoproteins in human parathyroid adenoma. APMIS 104:7-8, 789-796
CrossRef201
M. Saegusa, Y. Takano, Y. Kamata, I. Okayasu. (1996) Bcl-2 expression and allelic loss of thep53 gene in gastric carcinomas. Journal of Cancer Research and Clinical Oncology 122:7, 427-432
CrossRef202
Elizabeth Rosvold. (1996) Prognostic factors for patients with non-small cell lung cancer. Current Problems in Cancer 20:4, 272-279
CrossRef203
Da-Gong Wang, Aaros A. B. Barros D'Sa, Colin F. Johnston, Keith D. Buchanan. (1996) Oncogene expression in carotid body tumors. Cancer 77:12, 2581-2587
CrossRef204
M. M. Kennedy, Karen Blessing, George King, Keith M. Kerr. (1996) Expression of bcl-2 and p53 in Merkel Cell Carcinoma. The American Journal of Dermatopathology 18:3, 273-277
CrossRef205
Andreas Plettenberg, Johannes Pammer, Enwin Tschachler. (1996) Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene. Experimental Dermatology 5:3, 183-188
CrossRef206
BRAM TER HARMSEL, FRANK SMEDTS, JOHAN KUIJPERS, MARCEL JEUNINK, BAPTIST TRIMBOS, FRANS RAMAEKERS. (1996) BCL-2 IMMUNOREACTIVITY INCREASES WITH SEVERITY OF CIN: A STUDY OF NORMAL CERVICAL EPITHELIA, CIN, AND CERVICAL CARCINOMA. The Journal of Pathology 179:1, 26-30
CrossRef207
LOUKAS KAKLAMANIS, ADRIAN SAVAGE, NEIL MORTENSEN, PANAGIOTIS TSIOTOS, IPATIA DOUSSIS-ANAGNOSTOPOULOU, SIMON BIDDOLPH, RUTH WHITEHOUSE, ADRIAN L. HARRIS, KEVIN C. GATTER. (1996) EARLY EXPRESSION OF bcl-2 PROTEIN IN THE ADENOMA-CARCINOMA SEQUENCE OF COLORECTAL NEOPLASIA. The Journal of Pathology 179:1, 10-14
CrossRef208
Hidenaga Uesugi, Makoto Saegusa. (1996) Different expression of Bcl-2 protein in gastric adenomas and carcinomas. Pathology International 46:4, 274-280
CrossRef209
MASSIMO GEUNA, GIORGIO PALESTRO, LORENZA BIANCHI MALANDRONE, ANTONIO DURANDO, ANNA DEMURTAS, BRUNO TORCHIO, MARCO MASSOBRIO. (1996) Relationships between Proliferative Activity and Oncogene Expression in Human Breast Cancer. Annals of the New York Academy of Sciences 784:1 Challenges an, 555-563
CrossRef210
Cinzia Azzoni, Claudio Doglioni, Giuseppe Viale, Gianfranco Delle Fave, Michele De Boni, Pietro Caruana, Gabriella Ferraro, Cesare Bordi. (1996) Involvement of BCL-2 Oncoprotein in the Development of Enterochromaffin-like Cell Gastric Carcinoids. The American Journal of Surgical Pathology 20:4, 433-441
CrossRef211
A.N Crowson, C.M Magro, M.E Kadin, M Stranc. (1996) Differential expression of the bcl-2 oncogene in human basal cell carcinoma. Human Pathology 27:4, 355-359
CrossRef212
CLAUDIE C. FLOHIL, PATRICK A. JANSSEN, FRED T. BOSMAN. (1996) EXPRESSION OF BCL-2 PROTEIN IN HYPERPLASTIC POLYPS, ADENOMAS, AND CARCINOMAS OF THE COLON. The Journal of Pathology 178:4, 393-397
CrossRef213
Andreas Plettenberg, Johannes Pammer, Erwin Tschachler. (1996) Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene. Experimental Dermatology 5:2, 102-107
CrossRef214
Ingrid Moll, Frank Gillardon, Stefan Waltering, Monika Schmelz, Roland Moll. (1996) Differences of bcl-2 protein expression between Merkel cells and Merkel cell carcinomas. Journal of Cutaneous Pathology 23:2, 109-117
CrossRef215
Wenliang Wang, Henry Johansson, Ulla Bergholm, Erik Wilander, Lars Grimelius. (1996) Apoptosis and expression of the proto-oncogenesbcl-2 and p53 and the proliferation factor Ki-67 in human medullary thyroid carcinoma. Endocrine Pathology 7:1, 37-45
CrossRef216
Qi-Long Lu, Paul Abel, Christopher S Foster, El-Nasir Lalani. (1996) bcl-2: Role in epithelial differentiation and oncogenesis. Human Pathology 27:2, 102-110
CrossRef217
MUTSUO FURIHATA, HIROSHI SONOBE, YUJI OHTSUKI, MOTOYUKI YAMASHITA, MASAAKI MORIOKA, AKIHIRO YAMAMOTO, NAOTAMI TERAO, MORIMASA KUWAHARA, NOBUTA FUJISAKI. (1996) DETECTION OF p53 AND bcl-2 PROTEIN IN CARCINOMA OF THE RENAL PELVIS AND URETER INCLUDING DYSPLASIA. The Journal of Pathology 178:2, 133-139
CrossRef218
Gustavo Bruno Baretton, Joachim Diebold, Gregor Christoforis, Michael Vogt, Christian Müller, Karin Dopfer, Karin Schneiderbanger, Michael Schmidt, Udo Löhrs. (1996) Apoptosis and immunohistochemicalbcl-2 expression in colorectal adenomas and carcinomas: Aspects of carcinogenesis and prognostic significance. Cancer 77:2, 255-264
CrossRef219
Edward D. King, James Matteson, Stephen C. Jacobs, Natasha Kyprianou. (1996) Incidence of Apoptosis, Cell Proliferation and bcl-2 Expression in Transitional Cell Carcinoma of the Bladder. The Journal of Urology316-320
CrossRef220
Edward D. King, James Matteson, Stephen C. Jacobs, Natasha Kyprianou. (1996) Incidence of Apoptosis, Cell Proliferation and bcl-2 Expression in Transitional Cell Carcinoma of the Bladder: Association with Tumor Progression. The Journal of Urology 155:1, 316-320
CrossRef221
Kingsley J. Micklem. (1995) Novel leukaemia markers. Bioscience Reports 15:6, 463-468
CrossRef222
Makoto Saegusa, Yasuo Takano, Miki Hashimura, Youko Shoji, Isao Okayasu. (1995) The possible role of bcl–2 expression in the progression of tumors of the uterine cervix. Cancer 76:11, 2297-2303
CrossRef223
W. Kong Chan, Margaret M. Mole, David A. Levison, Richard Y Ball, Qi-Long Lu, Kirtika Patel, Andrew M. Hanby. (1995) Nuclear and cytoplasmicbcl-2 expression in endometrial hyperplasia and adenocarcinoma. The Journal of Pathology 177:3, 241-246
CrossRef224
François Paraf, Jean Gogusev, Yves Chrétien, Dominique Droz. (1995) Expression ofbcl-2 oncoprotein in renal cell tumours. The Journal of Pathology 177:3, 247-252
CrossRef225
M. ELLIS, M. RATHAUS, A. AMIEL, Y. MANOR, A. KLEIN, M. LISHNER. (1995) Monoclonal lymphocyte proliferation and bcl-2 rearrangement in essential mixed cryoglobulinaemia. European Journal of Clinical Investigation 25:11, 833-837
CrossRef226
Jon H Ritter, Carolyn M Dresler, Mark R Wick. (1995) Expression of bcl-2 protein in stage T1NOMO non-small cell lung carcinoma. Human Pathology 26:11, 1227-1232
CrossRef227
Olle Sangfelt, Anders Österborg, Dan Grandér, Elisabet Anderbring, Åke Öst, Håkan Mellstedt, Stefan Einhorn. (1995) Response to interferon therapy in patients with multiple myeloma correlates with expression of the Bcl-2 oncoprotein. International Journal of Cancer 63:2, 190-192
CrossRef228
V. Gorgoulis, P.P. Sfikakis, A. Karameris, H. Papastarnatiou, R. Trigidou, M. Veslemes, D.A. SpandidOs, P. Sfikakis, J. Jordanoglou. (1995) Molecular and Immunohistochemical Study of Class I Growth Factor Receptors in Squamous Cell Lung Carcinomas. Pathology - Research and Practice 191:10, 973-981
CrossRef229
Shi-Xu Jiang, Yuichi Sato, Sadahito Kuwao, Toru Kameya. (1995) Expression ofbcl-2 oncogene protein is prevalent in small cell lung carcinomas. The Journal of Pathology 177:2, 135-138
CrossRef230
I. BROCHERIOU, F. CARNOT, J. BRIERE. (1995) Immunohistochemical detection of bcl-2 protein in thymoma. Histopathology 27:3, 251-255
CrossRef231
PB Sugerman, BK Joseph, NW Savage. (1995) The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation. Oral Diseases 1:3, 172-188
CrossRef232
Jonathan C. Nesbitt, Joe B. Putnam, Garrett L. Walsh, Jack A. Roth, Clifton F. Mountain. (1995) Survival in early-stage non-small cell lung cancer. The Annals of Thoracic Surgery 60:2, 466-472
CrossRef233
G. TRONCONE, P. ZEPPA, A. VETRANI, A. D'ARCANGELO, F. FULCINITI, B. DIVITIIS, L. PALOMBINI. (1995) bel-2 protein in breast cancer cells obtained by fine needle aspiration (FNA): a preliminary report. Cytopathology 6:4, 219-225
CrossRef234
A. J. M. WATSON. (1995) manipulation of cell death - the development of novel strategies for the treatment of gastrointestinal disease. Alimentary Pharmacology & Therapeutics 9:3, 215-226
CrossRef235
Makoto Saegusa, Yasuo Takano, Isao Okayasu. (1995) Bcl-2 expression and its association with cell kinetics in human gastric carcinomas and intestinal metaplasia. Journal of Cancer Research and Clinical Oncology 121:6, 357-363
CrossRef236
Kim D. Steck, Timothy J. McDonnell, Adel K. El-Naggar. (1995) Flow cytometric analysis of apoptosis and BCL-2 in human solid neoplasms. Cytometry 20:2, 154-161
CrossRef237
Silvano Bosari, Laura Moneghini, Daniela Graziani, Arthur K.C Lee, John J Murray, Guido Coggi, Giuseppe Viale. (1995) bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas. Human Pathology 26:5, 534-540
CrossRef238
M.E.J.M. VERHAEGH, C.J.G. SANDERS, J.W. ARENDS, H.A.M. NEUMANN. (1995) Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer. British Journal of Dermatology 132:5, 740-744
CrossRef239
Gregory Y. Lauwers, Gregory V. Scott, Martin S. Karpeh. (1995) Immunohistochemical evaluation of bcl-2 protein expression in gastric adenocarcinomas. Cancer 75:9, 2209-2213
CrossRef240
Railf C. Bargou, Peter T. Daniel, Markus Y. Mapara, Kurt Bommert, Christian Wagener, Bianca Kallinich, Hans D. Royer, Bcrnd Dörken. (1995) Expression of thebcl-2 gene family in normal and malignant breast tissue: Lowbax-α expression in tumor cells correlates with resistance towards apoptosis. International Journal of Cancer 60:6, 854-859
CrossRef241
TSAILING WANG, JERZY LASOTA, CHERYL A. HANAU, MARKKU MIETTINEN. (1995) Bcl-2 oncoprotein is widespread in lymphoid tissue and lymphomas but its differential expression in benign versus malignant follicles and monocytoid B-cell proliferations is of diagnostic value. APMIS 103:7-8, 655-662
CrossRef242
J. Pammer, R. Horvat, W. Weninger, W. Ulrich. (1995) Expression of bcl-2 in Salivary Glands and Salivary Gland Adenomas. Pathology - Research and Practice 191:1, 35-41
CrossRef243
F. PEZZELLA, K. GATTER. (1995) What is the value of bcl-2 protein detection for histopathologists?. Histopathology 26:1, 89-93
CrossRef244
V. Zagonel, A. Pinto, D. Serraino, R. Babare, C. Sacco, M.C. Merola, M.G. Trovó, U. Tirelli, S. Monfardini. (1994) Lung cancer in the elderly. Cancer Treatment Reviews 20:4, 315-329
CrossRef245
Lorenzo Cerroni, Helmut Kerl. (1994) Aberrant bcl-2 protein expression provides a possible mechanism of neoplastic cell growth in cutaneous basal-cell carcinoma. Journal of Cutaneous Pathology 21:5, 398-403
CrossRef246
M. Carmen Saenz-Santamaria, Jon A. Reed, N. Scott McNutt, Christopher R. Shea. (1994) Immunohistochemical expression of BCL-2 in melanomas and intradermal nevi. Journal of Cutaneous Pathology 21:5, 393-397
CrossRef247
M. ZHAO, N-X. ZHANG, M. ECONOMOU, I. BLAHA, J.A. LAISSUE, A. ZIMMERMANN. (1994) Immunohistochemical detection of bcl-2 protein in liver lesions: bcl-2 protein is expressed in hepatocellular carcinomas but not in liver cell dysplasia. Histopathology 25:3, 237-245
CrossRef248
Helga A. Klein-Parker, Larry Warshawski, Victor A. Tron. (1994) Melanocytes in human skin express bcl-2 protein. Journal of Cutaneous Pathology 21:4, 297-301
CrossRef249
K. Segers, M. Ramael, S. Kumar Singh, E. Marck, J. Weyler, J. Meerbeeck, P. Vermeire. (1994) Immunoreactivity for bcl-2 protein in malignant mesothelioma and non-neoplastic mesothelium. Virchows Archiv 424:6, 631-634
CrossRef250
(1994) bcl-2 and Prognosis in Non-Small-Cell Lung Carcinoma. New England Journal of Medicine 330:24, 1757-1758
Full Text251
Gregory Y. Lauwers, Gregory V. Scott, James Hendricks. (1994) Immunohistochemical evidence of aberrantbcl-2 protein expression in gastric epithelial dysplasia. Cancer 73:12, 2900-2904
CrossRef252
Philip J. Barr, L. David Tomei. (1994) Apoptosis and Its Role in Human Disease. Bio/Technology 12:5, 487-493
CrossRef253
Silvana Pilotti, Paola Collini, Franco Rilke, Giorgio Cattoretti, Romualdo Del Bo, Marco A. Pierotti. (1994) Bcl-2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland. The Journal of Pathology 172:4, 337-342
CrossRef254
(1994) bcl-2 Protein in Non-Small-Cell Lung Carcinoma. New England Journal of Medicine 330:3, 221-221
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