Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis is one of the critical biological factors that correlate with the biological behavior of malignant tumors including cancer progression and clinical outcome. The present study was performed to clarify the clinical implications of BAG-1, a bcl-2 binding protein in esophageal squamous cell carcinoma (ESCC). Seventy-one cases with ESCC were investigated. Immunohistochemical study of BAG-1 was performed on resected specimens. The expression pattern of BAG-1 in nuclei and/or cytoplasm was analyzed and correlated with TNM classification, vessel invasion, survival period after surgery. BAG-1 expression in the nuclei was related to the depth of tumor invasion (P = 0.0381) but not to any other clinicopathologic parameters. The cytoplasmic staining pattern of BAG-1 exhibited no correlation with clinicopathologic parameters. Univariate analysis (P < 0.05), but not multivariate analysis, revealed significantly poor prognosis for ESCC cases exhibiting positive nucleic staining for BAG-1. Our data suggests that BAG-1 expression in the nuclei of ESCC plays an important role in tumor development and may be useful for predicting the prognosis after surgery.
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PMID:Nuclear BAG-1 expression is a biomarker of poor prognosis in esophageal squamous cell carcinoma. 1282 8

Clinical relevance and stage correlation of telomerase activity in well-differentiated papillary thyroid carcinoma (WD PTC) has not been well determined, as its reported activity could be due to the analysis of tumors with lymphocytic infiltrates or aggressive variants of papillary carcinomas. We conducted a prospective study of telomerase activity in WD PTC without inflammatory infiltrates and correlated it with clinical stage. Fifty WD PTCs were analyzed for telomerase activity by PCR-based TRAP (telomeric repeat amplification protocol) assay. Results were correlated with stage and other clinicopathologic variables. Twenty-one (42%) WD PTCs demonstrated telomerase activity. The enzyme was detected more frequently in stage III/IVa WD PTCs (p = 0.02) and in tumors with extra thyroidal extension (p = 0.04). The risk of presenting advanced disease (stage III/IVa) and extrathyroidal growth was significantly increased in telomerase-positive tumors (p = 0.01; odds ratio [OR] 4.4 [95%CI 1.3-14.7]) and (p = 0.04; OR 3.6 [95%CI 1.1-11.7]), respectively. Also, a correlation was found between telomerase activity and age. There was no correlation of telomerase activity with gender, histologic variant, tumor size, or cervical lymph node metastasis. Telomerase activity was observed in 42% of WD PTC and was detected more frequently in AJCC TNM stage III/IVa cases. This finding suggests that telomerase deregulation could be involved in tumor progression.
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PMID:Telomerase activity in well-differentiated papillary thyroid carcinoma correlates with advanced clinical stage of the disease. 1458 66

Orthotopic liver transplantation (OLT) is potentially curative for patients with early stage hepatocellular carcinoma (HCC). However, tumor progression before OLT remains a problem. Ninety-three patients were listed for transplantation with HCC or diagnosed with HCC following listing between March, 1997 and September, 2001. Modified TNM Stage was I/II in 82 patients and III in 11 patients. Seventy-one patients (76%) were transplanted with a median waiting time of 3.4 months, and 22 (24%) patients were delisted owing to tumor progression (14), noncompliance (5), and death from liver failure (3). Using a cox model competing risks approach, higher baseline alpha-fetoprotein (AFP) >or= 100 ng/mL was the only factor independently associated with a higher hazard rate of delisting owing to tumor progression (p = 0.00003), whereas four separate factors were independently associated with a lower hazard rate of transplantation: more recent listing year (1999-2001, p = 0.010), blood type O (p = 0.013), Stage I HCC (p = 0.029), and serum bilirubin < 4 mg/dL (p = 0.032). By logistic regression, AFP >/= 100 ng/mL was the only factor that significantly influenced the probability of delisting owing to tumor progression (p = 0.001). In conclusion, the initial AFP level may be useful along with tumor stage in defining an urgency score for liver transplant candidates with HCC.
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PMID:Competing risks analysis of predictors of delisting owing to tumor progression in liver transplant candidates with hepatocellular carcinoma. 1508 74

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict the prognosis. Therefore, novel predictive markers of the prognosis of esophageal cancer patients are awaited. The abnormality of the nucleotide excision repair (NER) is often involved in human cancers. Excision repair cross complementing 3 (ERCC3) contributes to NER. In esophageal cancer, ERCC3 expression has not been studied. Expression of ERCC3 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 43 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between the ERCC3 expression and the clinicopathological factors and prognosis of ESCC patients. ERCC3 expression level was significantly correlated with the pathologic stage, tumor size and local invasiveness (t-factor) in esophageal cancer tissues. Reduced expression of ERCC3 was accompanied with tumor progression (p=0.0049) and higher pathologic stage (p=0.020). Moreover, ESCC patients with low ERCC3 mRNA expression had significantly shorter post-operative survival time than those with high expression (p=0.0003). In esophageal cancer, reduced expression of ERCC3 was correlated with local tumor progression and poor prognosis after operation.
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PMID:Excision repair cross complementing 3 expression is involved in patient prognosis and tumor progression in esophageal cancer. 1537 7

Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and squamous cell carcinoma (SCC) antigen levels were assessed to determine if their levels are useful for staging esophageal cancer preoperatively and for predicting patient survival after esophagectomy. Hence their seropositivity was investigated for a correlation with resectability, clinicopathologic parameters of tumor progression, and treatment outcomes in patients with unresectable esophageal cancer ( n = 63) and those undergoing esophagectomy for resectable disease ( n = 267). Abnormal elevation of serum SCC antigen levels showed a significant correlation with resectability ( p< 0.0001), depth of tumor invasion ( p < 0.0001), lymph node status ( p = 0.0015), TNM stage ( p < 0.0001), lymphatic invasion ( p = 0.0019), blood vessel invasion ( p = 0.0079), and poor survival after esophagectomy ( p = 0.0061). A significant relation ( p = 0.0145) was found between elevated serum CEA levels and distant metastasis, whereas the seropositivity of CA 19-9 showed no association with resectability, tumor progression, or patient survival. These results indicate that abnormal elevation of serum SCC antigen is a useful predictor of advanced esophageal cancer associated with poor survival after esophagectomy.
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PMID:Clinical significance of serum carcinoembryonic antigen, carbohydrate antigen 19-9, and squamous cell carcinoma antigen levels in esophageal cancer patients. 1538 68

E-cadherin-mediated and desmosomal cell-cell adhesion have been implicated in the suppression of invasive and metastatic behavior of squamous cell carcinomas. Whether the adhaerens junction represented by E-cadherin and the desmosomes interplay or have distinct and separate roles in squamous cell cancer progression is still unclear. We have studied a cohort of 200 primary tumors and 56 lymph node metastases from different anatomic sites of the head and neck region for changes in synthesis of E-cadherin, desmoplakin and desmoglein by immunohistochemistry (IHC). Selected cases were studied by indirect immunofluorescence (IIF) and electron microscopy (EM). Only frozen sections were evaluated since they gave stronger and reproducible staining results. IHC data obtained were compared to clinical parameters. While some reduction in immunostaining was found in virtually all invasive tumors, at least partial expression, including that of E-cadherin, persisted in most late stage tumors and in lymph node metastases. Reduced desmosomal staining correlated with desmosomes reduced in numbers, size or in structural defects by EM analysis. By univariate analysis, reduction in synthesis of both E-cadherin and the desmosomal components that were generally linked (i.e., they showed positive rank correlations) were significantly associated with clinical parameters including overall and disease-free survival. However, by multivariate analysis including a Cox proportional hazards regression model (backward selection), the desmosomal components were not significant as independent prognostic factors. By contrast, E-cadherin was strongly associated with patient prognosis. In line with the highly significant association of reduced E-cadherin synthesis with an increased relative risk of follow up events, i.e., regional lymph node (p = 0.0007) and distant metastasis (p < 0.0001), as well as local recurrences (p < 0.0001), the prognostic strength of E-cadherin was independent of and stronger than histological grading, N stage, tumor site, and even stronger than the TNM stage. Based on these results, evaluation of E-cadherin in squamous cell carcinomas by immunostaining is recommended as a significant prognostic marker.
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PMID:E-cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: a comparison of E-cadherin with desmosomal components. 1560 7

As the biological behaviour of even early stage renal cell cancer (RCC) strongly correlates with tumor size, it has been argued that the inclusion of RCC up to a maximum diameter of 7 cm into a common subgroup classified as T1 according to the 5th edition of the TNM system would not adequately represent the different biological aggressiveness of these malignancies. Taking this into account, the TNM classification, which now categorizes T1 RCC as T1a and T1b according to a cutoff size of 4 cm, was recently modified. However, only a few larger investigations, mainly based on univariate statistical analyses, that support the suitability of this cutoff are at present available from the literature. Therefore, it was the aim of the present investigation to determine the tumor size that best separates patients with low responses from those with high risk for tumor progression by univariate (log rank test) and multivariate (Cox regression model) statistical analyses. Between 1981 and 2000, 652 patients (443 males and 209 females) underwent tumor nephrectomy in our clinic for the diagnosis of RCC. Of these, 243 patients revealed primary tumors with a local growth not extending beyond the renal capsula at the time of surgery. For the different cutoff levels (starting from 2 cm in increments of 1 cm up to 8 cm) that were selected to subdivide the patients into groups according to the maximum tumor diameter, the correlation between tumor size and overall survival was determined by univariate and multivariate statistical analyses. It became evident that although during univariate analysis the prognostic value of a cutoff size of 4 cm was confirmed, multivariate analysis identified the highest relative risk for cause-specific death (2.93) for patients having tumors larger than 5 cm in maximum diameter. Therefore, the 5 cm cutoff seems to best determine the clinical prognosis of patients undergoing tumor nephrectomy for early stage RCC. The present study demonstrates the need for multivariate statistical approaches when the latest modification of the TNM classification system is critically evaluated.
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PMID:Impact of tumor size on the long-term survival of patients with early stage renal cell cancer. 1572 58

Pancreatic cancer has an abysmal prognosis because of late diagnosis and lack of effective therapeutics. New drugs are desperately needed. The present study determined the effect of the LTB4 receptor antagonist, LY293111, on tumor growth and metastases in a fluorescent orthotopic model of pancreatic cancer. Pancreatic cancer cells (S2-013) with stable expression of enhanced green fluorescent protein were implanted into the duodenal pancreatic lobe of athymic mice. Animals were allocated to four groups (eight mice per group): control (no treatment); LY293111; gemcitabine; and LY293111 + gemcitabine. Monitoring of the surgical procedure and follow-up examinations at 2, 3, and 4 weeks after implantation to monitor tumor growth and metastases were performed using a fluorescence microscope and the reversible skin-flap technique. A staging and scoring system was developed to evaluate tumor progression, based on the TNM classification. Control animals developed end-stage disease with invasive cancer, metastases, and cachexia. Tumor growth and incidence of metastases were significantly reduced in all treated mice. However, combined treatment with LY293111 and gemcitabine was most effective. LY293111 is a novel therapeutic agent for pancreatic cancer, which improves the efficacy of gemcitabine. It is well tolerated and can be administered orally and, therefore, provides a new hope for patients suffering from pancreatic adenocarcinoma.
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PMID:LY293111 improves efficacy of gemcitabine therapy on pancreatic cancer in a fluorescent orthotopic model in athymic mice. 1596 19

The angiogenic factor called vascular endothelial growth factor (VEGF)-D is a ligand for VEGF receptor-2 (VEGFR-2/KDR) and receptor-3 (VEGFR-3/Flt-4). It is implicated in the development of lymphatic vessels and promotion of lymphatic metastasis. The purpose of this study was to investigate the prognostic significance of VEGF-D expression in patients with gastric carcinoma. We assessed the expression of VEGF-D in gastric carcinoma by immunohistochemistry on 143 consecutive patients' stored sections and evaluated the lymphatic vessel count (LVC) in tumors using the novel selective lymphatic endothelium marker D2-40. VEGF-D expression was observed in 55 (39%) tumor sections. The expression of VEGF-D correlated significantly with tumor size, T of the TNM classification, lymphatic and venous system invasion, LVC, lymph node metastasis, M of TNM, and pTNM stage. Multivariate analysis indicated that VEGF-D expression was an independent prognostic factor for both relapse-free survival (RFS) and overall survival (OS). Our data indicate the involvement of VEGF-D in tumor progression via lymphoangiogenic pathways. Practically, VEGF-D expression can be useful for predicting RFS and OS in patients with gastric carcinoma.
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PMID:Prognostic significance of vascular endothelial growth factor D in gastric carcinoma. 1631 50

Significant advances have been made in all aspects of care relating to colorectal cancer. Although surgery will likely remain the mainstay of definitive treatment for the majority of colorectal malignancies, a better understanding of tumor progression and biology will help guide the choice of surgical therapy to best achieve a curative resection. Additionally, advances in the use of neoadjuvant and adjuvant therapies should continue to increase disease-free and overall survival when combined with appropriate operative resection. Although TNM staging remains our strongest tool at this point for establishing prognosis and directing therapy, expansion of our knowledge of the molecular events underlying colorectal tumorigenesis undoubtedly will lead to the refinement of our current staging and prognostic systems.
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PMID:Staging and prognosis of colon cancer. 1638 54


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