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SEÇİNTİ İE, AKINCIOĞLU E, KANDEMİR O. Beclin 1 (otofaji belirteci), p53 mutasyonu, Ki-67 proliferasyon indeksi, tümör nekrozu ve mikrovasküler invazyonun böbrek hücreli karsinomlarda prognoz üzerindeki etkisi ve bunların bilinen prognostik parametrelerle ilişkisi. KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNIVERSITESI TIP FAKÜLTESI DERGISI 2020. [DOI: 10.17517/ksutfd.794679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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Zhang W, Li X, Xu T, Ma M, Zhang Y, Gao MQ. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis. Exp Cell Res 2016; 349:45-52. [DOI: 10.1016/j.yexcr.2016.09.016] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 09/11/2016] [Accepted: 09/24/2016] [Indexed: 01/11/2023]
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Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes. Sci Rep 2016; 6:27462. [PMID: 27272504 PMCID: PMC4895242 DOI: 10.1038/srep27462] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 05/19/2016] [Indexed: 01/03/2023] Open
Abstract
Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment.
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Zhang L, Yao L, Li X, Jewett MA, He Z, Zhou L. Natural history of renal cell carcinoma: An immunohistochemical analysis of growth rate in patients with delayed treatment. J Formos Med Assoc 2016; 115:463-9. [DOI: 10.1016/j.jfma.2015.05.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 05/13/2015] [Accepted: 05/13/2015] [Indexed: 01/12/2023] Open
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Abstract
Objective: To review the natural history and growth kinetics of small renal masses (SRMs). Data Sources: The literature concerning natural history and growth kinetics of SRMs was collected from PubMed published from 1990 to 2014. Study Selection: We included all the relevant articles on the active surveillance (AS) or delayed treatment for SRMs in English, with no limitation of study design. Results: SRMs under AS have a slow growth potential in general. The mean linear growth rate is 0.33 cm/year, the mean volumetric growth rate is 9.48 cm3/year. The rate of metastasis during AS is below 2%. Some factors are associated with the growth rate of SRMs, including tumor grade, histological subtype, initial tumor size, age, radiographic characteristics, and molecular markers. No definite predictor of growth rate of SRMs is defined at present. SRMs with high tumor grade and the subtype of clear cell renal cell carcinoma may have aggressive growth potential. Conclusions: AS is a reasonable choice for elderly patients with SRMs, who are at high risk from surgery. Progression during observation is the biggest concern while performing AS. There is no definite predictor of progression for SRMs under AS. Percutaneous renal biopsy providing immunohistological and genic biomarkers may improve the understanding of natural history of SRMs.
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Affiliation(s)
| | - Xue-Song Li
- Department of Urology, Peking University First Hospital, Beijing 100034, China
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Growth Pattern of Clear Cell Renal Cell Carcinoma in Patients with Delayed Surgical Intervention: Fast Growth Rate Correlates with High Grade and May Result in Poor Prognosis. BIOMED RESEARCH INTERNATIONAL 2015; 2015:598134. [PMID: 26421295 PMCID: PMC4573233 DOI: 10.1155/2015/598134] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2014] [Accepted: 03/08/2015] [Indexed: 11/18/2022]
Abstract
Objectives. Previous studies revealed an unclear correlation between the growth rate of renal cell carcinoma (RCC) and tumor grade and did not focus on certain histological subtype. This report investigated the correlation between the growth rate and tumor grade in clear cell RCC (ccRCC). Methods. We reviewed 60 patients with 61 ccRCC confirmed by delayed surgeries after at least 12 months of active surveillance. The linear growth rate (LGR), volumetric growth rate (VGR), and volume doubling time (VDT) were calculated, and their correlations with clinicopathologic characteristics were analyzed. Results. The mean LGR, VGR, and VDT were 0.86 (range 0–4.74) cm/year, 20.96 (range 0.31–211.93) cm3/year, and 667 (range 33–3321) days, respectively. ccRCCs with high grade had greater LGR (P < 0.001) and VGR (P = 0.001) and lower VDT (P = 0.017) than ccRCCs with low grade. Grade (OR = 5.185, P = 0.004) was the only independent risk factor of LGR >0.5 cm/year, and grade (OR = 3.006, P = 0.046) and initial size (OR = 0.392, P = 0.004) were independent risk factors of VDT <1 year. Five patients developed metastasis after surgery with LGR >0.5 cm/yr altogether; of them, four had cancer-related death by the last follow-up. Conclusions. Fast growth rate of ccRCC is significantly correlated with high tumor grade and may result in poor prognosis, especially for those with LGR >0.5 cm/yr.
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Small renal cell carcinomas--how dangerous are they really? Results of a large multicenter study. Eur J Cancer 2013; 50:739-45. [PMID: 24321262 DOI: 10.1016/j.ejca.2013.11.020] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2013] [Revised: 10/27/2013] [Accepted: 11/19/2013] [Indexed: 12/18/2022]
Abstract
AIM OF THE STUDY Modern diagnostic ultrasound and cross-sectional imaging has enabled the detection of increasing numbers of renal tumours. The aim of this study was to investigate the tumour- and patient-specific characteristics and prognosis of small renal cell carcinomas (RCCs) after surgical resection. METHODS The study included 2197 patients who underwent surgical resection of histologically confirmed RCC ⩽ 4 cm between 1990 and 2011. Median (mean) follow-up was 56.2 (65.5) months. RESULTS At the time of surgery, tumours were staged as pT ⩾ 3a in 175 (8.0%) cases, 134 (6.2%) were poorly differentiated and 75 (3.5%) were metastasised. The larger the tumour size, the higher was the risk of presenting with stage pT ⩾ 3a (p<0.001), poor tumour differentiation (p = 0.004), microscopic vascular involvement (p = 0.001) and collecting system invasion (p = 0.03). The 5-year cancer-specific survival (CSS) rate was 93.8% for stage pT1a versus 79.4% for stage pT ⩾ 3a (p<0.001), and it was 93.7% for G1-2 versus 76.8% for G3-4 differentiation (p<0.001). Multivariate analysis identified age in years (hazard ratio (HR) 1.04, p<0.001), metastatic disease (HR 12.5, p < 0.001), tumour differentiation (HR 2.8, p<0.001) and non-clear cell histology (HR 0.51, p = 0.02) as independent prognosticators for CSS in patients with small RCC. Interestingly, the 5-year cancer-specific mortality rate for pT1a N/M0 patients was 5.8%. CONCLUSIONS This large multicenter study has clearly shown that, though most small RCC have a low pathological stage and a good prognosis, there is also a small but significant subgroup of these tumours that are already locally advanced or poorly differentiated.
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Gao MQ, Kim BG, Kang S, Choi YP, Park H, Kang KS, Cho NH. Stromal fibroblasts from the interface zone of human breast carcinomas induce an epithelial-mesenchymal transition-like state in breast cancer cells in vitro. J Cell Sci 2010; 123:3507-14. [PMID: 20841377 DOI: 10.1242/jcs.072900] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Fibroblasts were extracted from tissue in tumor burden zones, distal normal zones and interface zones between tumor and normal tissue of human breast carcinomas, and the corresponding fibroblasts were designated as cancer-associated fibroblasts (CAFs), normal zone fibroblasts (NFs) and interface zone fibroblasts (INFs). The crosstalk between three types of fibroblasts and breast cancer cells was evaluated using an in vitro direct co-culture model. We found that INFs grew faster and expressed higher levels of fibroblast activation protein than did NFs and CAFs. Compared with CAFs and NFs, INFs grown with breast cancer cells were significantly more effective in inducing an epithelial-mesenchymal transition (EMT) in cancer cells, as indicated by induction of vimentin and N-cadherin and downregulation of E-cadherin. This EMT process was also accompanied by activation of extracellular signal-regulated kinase (ERK) and modulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) expression. Additionally, INFs promoted breast cell migration to a larger extent compared with NFs and CAFs. Taken together, these findings indicate that INFs isolated from the tumor interface zone exhibited more robust biological modulatory activity than did NFs and CAFs isolated from normal and tumor zones of the same tumor tissue, suggesting that the interface zone of the tumor represents a dynamic region vital to tumor progression.
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Affiliation(s)
- Ming-Qing Gao
- Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea
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Toge H, Inagaki T, Kojimoto Y, Shinka T, Hara I. Angiogenesis in renal cell carcinoma: The role of tumor-associated macrophages. Int J Urol 2009; 16:801-7. [DOI: 10.1111/j.1442-2042.2009.02377.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Jewett MAS, Zuniga A. Renal tumor natural history: the rationale and role for active surveillance. Urol Clin North Am 2009; 35:627-34; vii. [PMID: 18992616 DOI: 10.1016/j.ucl.2008.07.004] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Renal cell carcinoma (RCC) is the most common malignancy of the kidney. Despite widespread treatment at diagnosis, overall mortality rates associated with RCC have not decreased. Partly because of the more frequent use of abdominal imaging, diagnosis as an incidental finding has increased. The largest increase in incidence is in tumors smaller than 4 cm, termed small renal masses (SRMs). SRMs that are RCC may frequently be growth slowly and have a low risk of early progression. Initial active surveillance with delayed treatment for progression for selected patients should be considered. This should result in an overall decrease in treatment burden and cost saving.
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Affiliation(s)
- Michael A S Jewett
- Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital and the University Health Network, University of Toronto, 610 University Avenue, 3-124, Toronto, Ontario, Canada M5G 2C4.
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Naxerova K, Bult CJ, Peaston A, Fancher K, Knowles BB, Kasif S, Kohane IS. Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers. Genome Biol 2008; 9:R108. [PMID: 18611264 PMCID: PMC2530866 DOI: 10.1186/gb-2008-9-7-r108] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2008] [Revised: 05/31/2008] [Accepted: 07/08/2008] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND In recent years, the molecular underpinnings of the long-observed resemblance between neoplastic and immature tissue have begun to emerge. Genome-wide transcriptional profiling has revealed similar gene expression signatures in several tumor types and early developmental stages of their tissue of origin. However, it remains unclear whether such a relationship is a universal feature of malignancy, whether heterogeneities exist in the developmental component of different tumor types and to which degree the resemblance between cancer and development is a tissue-specific phenomenon. RESULTS We defined a developmental landscape by summarizing the main features of ten developmental time courses and projected gene expression from a variety of human tumor types onto this landscape. This comparison demonstrates a clear imprint of developmental gene expression in a wide range of tumors and with respect to different, even non-cognate developmental backgrounds. Our analysis reveals three classes of cancers with developmentally distinct transcriptional patterns. We characterize the biological processes dominating these classes and validate the class distinction with respect to a new time series of murine embryonic lung development. Finally, we identify a set of genes that are upregulated in most cancers and we show that this signature is active in early development. CONCLUSION This systematic and quantitative overview of the relationship between the neoplastic and developmental transcriptome spanning dozens of tissues provides a reliable outline of global trends in cancer gene expression, reveals potentially clinically relevant differences in the gene expression of different cancer types and represents a reference framework for interpretation of smaller-scale functional studies.
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Affiliation(s)
- Kamila Naxerova
- Children's Hospital Informatics Program, Harvard-MIT Division of Health Sciences and Technology, Longwood Avenue, Boston, MA 02115, USA
| | - Carol J Bult
- The Jackson Laboratory, Main Street, Bar Harbor, ME 04609, USA
| | - Anne Peaston
- The Jackson Laboratory, Main Street, Bar Harbor, ME 04609, USA
| | - Karen Fancher
- The Jackson Laboratory, Main Street, Bar Harbor, ME 04609, USA
| | | | - Simon Kasif
- Children's Hospital Informatics Program, Harvard-MIT Division of Health Sciences and Technology, Longwood Avenue, Boston, MA 02115, USA
- Department of Biomedical Engineering, Boston University, Cummington Street, Boston, MA 02215, USA
| | - Isaac S Kohane
- Children's Hospital Informatics Program, Harvard-MIT Division of Health Sciences and Technology, Longwood Avenue, Boston, MA 02115, USA
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Affiliation(s)
- Paul L Crispen
- Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA 19111, USA
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Remzi M, Ozsoy M, Klingler HC, Susani M, Waldert M, Seitz C, Schmidbauer J, Marberger M. Are Small Renal Tumors Harmless? Analysis of Histopathological Features According to Tumors 4 Cm or Less in Diameter. J Urol 2006; 176:896-9. [PMID: 16890647 DOI: 10.1016/j.juro.2006.04.047] [Citation(s) in RCA: 240] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2005] [Indexed: 11/20/2022]
Abstract
PURPOSE Small renal tumors detected incidentally are considered to have less aggressive potential. This assumption is mainly based on the low tendency to increase in size on serial imaging studies, but histopathological parameters of progression in larger patient series are scant. MATERIALS AND METHODS We reviewed data of 287 tumor bearing kidneys in which solid tumors 4 cm or less in diameter were detected by cross-sectional imaging and subsequently removed surgically. Tumor size as documented by preoperative computerized tomography was correlated to histological diagnosis, and in cases of malignancy correlated to tumor type, pathological TNM stage and nuclear (Fuhrman) grade. With multifocal lesions the largest single tumor was considered the reference lesion but multifocality was also considered a separate parameter. RESULTS At a mean tumor diameter of 2.94 +/- 0.87 cm 65 (22.6%) tumors were 2 cm or less, 103 (35.9%) were 2.1 to 3.0 cm and 119 (41.5%) were 3.1 to 4 cm in diameter. A total of 56 (19.5%) tumors were benign with no correlation to tumor size (Pearson test p = 0.660). Renal cell cancer was found in 227 (79.1%) patients with 159 (70.0%) clear cell, 47 (20.7%) papillary, 11 (4.8%) chromophobe and 10 others with no correlation to tumor diameter. Of the kidneys 31 (13.6%) had multifocal renal cell carcinoma, with a significant correlation to larger tumor diameter (linear regression p = 0.048) and papillary renal cell carcinoma subtype (linear regression p = 0.018). Two (4.2%), 4 (5%) and 25 (25.5%) cases of renal cell carcinoma 2 cm or less, 2.1 to 3 cm and 3.1 to 4 cm in diameter had Fuhrman grade G3/4, respectively (Pearson p = 0.0007). Advanced stage (pT3a or greater) was documented in 2 (4.2%), 12 (14.9%) and 35 (35.7%) cases for the same categories, respectively (p = 0.0023). Whereas distant metastases were diagnosed in only 4 patients with renal cell carcinoma with tumors 3 cm or less, distant metastases were in 10 (8.4%) patients with tumors 3.1 to 4 cm (p = 0.045). CONCLUSIONS The aggressive potential of small renal cell carcinoma increases dramatically beyond a tumor diameter of 3 cm. Given the difficulty in measuring tumor diameters reliably with sequential imaging studies, the threshold for selecting patients for a surveillance strategy should be set well under this parameter.
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Affiliation(s)
- Mesut Remzi
- Department of Urology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
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Nagatsuka H, Hibi K, Gunduz M, Tsujigiwa H, Tamamura R, Sugahara T, Sasaki A, Nagai N. Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas. J Oral Pathol Med 2005; 34:70-6. [PMID: 15641985 DOI: 10.1111/j.1600-0714.2004.00227.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Intratumoral blood vessels are known to play an important role in cancer growth and metastasis. The discrepancy in previous reports using various endothelial markers individually suggested us to investigate both normal and various tumor areas with a wide panel of vascular markers. METHODS Here, we used a panel of three antibodies (CD31, CD34, and endoglin) as blood vessel markers to investigate the distribution and properties of blood vessels in normal oral tissues and squamous cell carcinomas. RESULTS Many microvessels with strong remodeling activity as well as undifferentiated tumoral vascular endothelial cells and immature endothelial cells were present in the cancer cell nest and marginal area of cancer infiltration. Our results showed different vascular distribution patterns using various immunostaining markers in normal and tumoral tissues. CONCLUSION Vascular distribution and properties of endothelial cells appear to be closely associated with metastasis.
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Affiliation(s)
- Hitoshi Nagatsuka
- Department of Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama University, Shikatacho 2-5-1, Okayama, Japan
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Davidson K, Percy C, Rennick AJ, Pat BK, Li J, Nicol D, Johnson DW, Gobe GC. Comparative Analysis of Caspase Activation and Apoptosis in Renal Tubular Epithelial Cells and Renal Cell Carcinomas. ACTA ACUST UNITED AC 2005; 99:e112-20. [PMID: 15711100 DOI: 10.1159/000083926] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2004] [Accepted: 10/12/2004] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Treatment of renal cell carcinoma (RCC) is limited by its resistance to conventional chemotherapies. This may occur, in part, from resistance to apoptosis. The role of caspase activation in apoptosis resistance in treated RCCs was investigated. METHODS Two human RCC cell lines (ACHN and SN12K1) and renal tubular epithelial cells (HK2) were treated with 5-fluorouracil (0.2-20 microg/ml) or cisplatin (1-100 microM). Activation of caspase-3 and -2 was analysed and compared with levels of apoptosis. Caspase function was analysed using pan-caspase inhibition (z-VAD-fmk) and caspase-2 inhibition (z-VDVAD-fmk). RESULTS RCC apoptosis was significantly lower (p < 0.05) than in HK2s after treatment, confirming their chemoresistance. Pro-caspase-3 (32 kDa) was detected in all cell lines. Cleaved caspase-3 (19 kDa) was not detected by Western immunoblots in treated RCCs and only minimal activated caspase-3 was detected in treated RCCs using immunohistochemistry. All cells had pro-caspase-2 (48 kDa) and the activated form (33 kDa) appeared in all treated cells. Caspase inhibition caused a reduction in, but not negation of, therapy-induced apoptosis in HK2s and RCCs (p < 0.05 for HK2s and ACHN cells), indicating that a caspase activation pathway must occur in RCC apoptosis but this pathway does not act via caspase-3 cleavage. Inhibition of caspase-2 reduced apoptosis only in HK2s, indicating that the activated caspase-2, identified in treated RCCs, was not responsible for their apoptosis induction. CONCLUSION Specific differences in caspase-3 and -2 activation were identified in renal tubular epithelium and RCCs after chemotherapy. Identification of RCC-specific caspase inactivation or redundancy may explain, in part, the resistance of RCCs to cancer therapies and may be useful in targeting apoptotic pathways to overcome RCC resistance to treatment.
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Affiliation(s)
- Keryn Davidson
- Molecular and Cellular Pathology, School of Medicine, University of Queensland, Herston, Australia
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Kato M, Suzuki T, Suzuki Y, Terasawa Y, Sasano H, Arai Y. Natural history of small renal cell carcinoma: evaluation of growth rate, histological grade, cell proliferation and apoptosis. J Urol 2004; 172:863-6. [PMID: 15310984 DOI: 10.1097/01.ju.0000136315.80057.99] [Citation(s) in RCA: 132] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE We investigated the natural history of incidentally discovered small renal cell carcinomas (RCCs), and we evaluated growth rate, apoptosis, cell proliferation and histological grade. MATERIALS AND METHODS A total of 18 patients with RCCs extirpated after at least 12 months of observation were reviewed retrospectively. The period of observation ranged from 12 to 63 months (median 22.5). Median patient age was 56.5 years, ranging from 37 to 71. Annual tumor growth rate was calculated from diameter obtained from computerized tomography or ultrasound. Cell proliferation and apoptosis were assessed by immunostaining using Ki-67 and TUNEL. RESULTS Average tumor growth rate was 0.42 cm per year (standard error 0.09, 95% confidence interval 0.24 to 0.61). Of the 18 tumors 7 were grade 1, 8 were grade 2 and 3 were grade 3. Tumor growth rate and Ki-67 positive ratio were not correlated. In contrast, growth rate and positive ratio of TUNEL were significantly correlated. A significant difference in growth rate was observed between grade 2 and 3 tumors but not between grade 1 and 2 tumors. CONCLUSIONS The growth rate of RCCs correlates with apoptosis and grade. Most incidentally found RCCs are slow growing. However, those with certain histopathological features can grow rapidly and have a poor prognosis. More attention should be given to the observation of small renal masses.
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Affiliation(s)
- Masanori Kato
- Department of Urology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ward, Sendai 980-8574, Japan.
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Xu MH, Deng CS, Zhu YQ, Lin J. Role of inducible nitric oxide synthase expression in aberrant crypt foci-adenoma-carcinoma sequence. World J Gastroenterol 2003; 9:1246-50. [PMID: 12800233 PMCID: PMC4611793 DOI: 10.3748/wjg.v9.i6.1246] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the expression of inducible nitric oxide synthase (iNOS) in aberrant crypt foci (ACF) -adenoma-carcinoma sequence and its relation with tumor cell apoptosis, proliferation and angiogenesis.
METHODS: The expression of iNOS, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) in different stages of colorectal cancer were studied by immunohistochemical method from 30 normal tissues, 30 nonhyperplastic ACF, 30 hyperplastic ACF, 30 dysplastic ACF, 30 adenomas and 60 carcinomas. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method using an Apop Tag in situ detection kit.
RESULTS: The immunoreactivity of iNOS significantly increased in the transition from hyperplastic ACF to dysplastic ACF. This transition was associated with a significant decrease in the apoptotic index (AI) (0.73 ± 0.37 vs 0.61 ± 0.35, P < 0.05) and significant increases in the PCNA labeling index (LI) (27.3 ± 2.80 vs 40.3 ± 3.11, P < 0.01) and microvessel density (MVD) (55 ± 11.5 vs 70 ± 13.2, P < 0.01). The expression of iNOS was in low levels and positively correlated with PCNA-LI (r = 0.812, P < 0.01) and MVD (r = 0.863, P < 0.01) during transition from normal mucosa to nonhyperplastic ACF and hyperplastic ACF. The expression of iNOS was in high levels and positively correlated with AI (r = 0.901, P < 0.01) after transition from hyperplastic ACF to dysplastic ACF, adenoma and carcinoma.
CONCLUSION: The results suggest that the transition from hyperplastic ACF to dysplastic ACF may be a crucial step in the ACF-adenoma-carcinoma sequence, in which iNOS plays an important role by regulating tumor cell apoptosis, proliferation and angiogenesis.
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Affiliation(s)
- Mei-Hua Xu
- Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province China.
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