Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ductal carcinoma in situ (DCIS) is a heterogeneous malignant condition of the breast with an excellent prognosis. Until recently mastectomy was the standard treatment. As the results of the National Surgical Adjuvant Breast and Bowel Project-17 trial and the introduction of the Van Nuys Prognostic Index (VNPI) less radical therapies are used. Objectives are to identify clinicopathologic and biologic factors that may predict outcome. Cases of DCIS diagnosed in two Belgian University Centers were included. Paraffin-embedded material and Hematoxylin and Eosin stained slides of DCIS cases were reviewed and tumor size, margin width, nuclear grade, and comedo necrosis were assessed. Molecular markers (estrogen receptor, progesterone receptor, HER1-4, Ki67, and c-myc) were assayed immunohistochemically. Applied treatment strategies were correlated with the prospective use of the VNPI score. Kaplan-Meier survival plots were generated with log-rank significance and multiple regression analysis was carried out using Cox proportional hazards regression analysis; 159 patients were included with a median age of 54 years (range 29-78); 141 had DCIS and 18 DCIS with microinvasion. The median time of follow-up was 54 months (range 5-253). Twenty-three patients developed a recurrence (14.5%). The median time to recurrence was 46 months (range 5-253). Before the introduction of the VNPI, 37.5% of the DCIS patients showed a recurrence while thereafter 6.7% recurred (p < 0.005). Two recurrences occurred in the VNPI group I (7.1%); seven in the VNPI group II (8.5%) (median time to recurrence 66.3 months) and 14 in the VNPI group III (28.5%) (median time to recurrence 40.2 months) (disease-free survival [DFS]: p < 0.05). A Cox proportional hazards regression analysis indicated that tumor size, margin width, pathologic class, and age were independent predictors of recurrence, but none of the studied molecular markers showed this. Overexpression of HER4 in the presence of HER3 was found to be associated with a better DFS (p < 0.05). This study confirms the value of the VNPI score and questions the benefit of an aggressive approach in the low-risk DCIS lesions. Independent predictors for recurrence included size, margin width, pathologic class, and age, but none of the molecular markers were part of it. Overexpression of HER4 in the presence of HER3 was associated with a better DFS.
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PMID:Prognostic significance of oncogenic markers in ductal carcinoma in situ of the breast: a clinicopathologic study. 1929 96

Preoperative chemoradiotherapy is recommended for locally advanced rectal cancer (UICC stage II/III). We recently demonstrated that responsive and nonresponsive tumors showed differential expression levels of 54 genes. In this follow-up study, we investigated the relationship between this gene set and disease-free (DFS) and overall survival (OS). Pretherapeutic biopsies from 30 participants in the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group were analyzed using gene expression microarrays. Statistical analysis was performed to identify differentially expressed genes between recurrent and nonrecurrent tumors and to correlate these changes with disease recurrence and outcome. After a median follow-up of 59 months, seven of eight patients with recurrent disease was a nonresponder, and one responsive tumor recurred. Response to chemoradiotherapy was significantly correlated with an improved DFS (log rank P=0.028), whereas OS did not differ significantly (P=0.11). Applying a class comparison analysis, we identified 20 genes that were differentially expressed between recurrent and nonrecurrent tumors (P<0.001). Analyzing the first two principal components of the 54 genes previously identified to predict response, we observed that this response signature correlated with an increased risk of cancer recurrence. These data suggest that the genetic basis of local response also affects the genetic basis of tumor recurrence. Genes that are indicative of nonresponse to preoperative chemoradiotherapy might also be linked to an increased risk of tumor recurrence.
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PMID:Preoperative chemoradiotherapy in locally advanced rectal cancer: correlation of a gene expression-based response signature with recurrence. 1938 20

We described the results of a hypofractionated regimen (HFRT) in a cohort of elderly patients (36 subjects) with stage I-II non-small-cell-lung cancer (NSCLC), tumor size> or =3 cm and ineligible for surgery. HFRT was delivered in 20 daily fractions of 3 Gy per fraction with a total dose of 60 Gy. The median PTV was 145 cm(3). The primary purpose of study was to estimate the local tumor control at 2 years as well as the modifications in the lung function parameters at 6 and 12 months. The local tumor control was 63.9% at 2 years. The incidence of distant recurrence rate at 2 years was 50%. The overall-survival (OS), the cause-specific-survival (CSS) and the disease-free-survival (DSF) at 2 years were 55.6, 57.1, and 38.9%, respectively. The median OS, CSS, and DFS was 25.4 (CI 95% 21.7-32.9), 26.7 (CI 95% 22.5-33.5) and 23.4 months (CI 95% 18.6-30.1), respectively. The two clinical parameters with a positive influence on OS were a KPS> or =90 (HR 1.16; p=0.013) and tumor size< or =4 cm (HR 0.763; p=0.011). No grade 3-4 acute toxicity was reported. No significant change in lung function parameters was measured at 6 and 12 months. For patients with larger or centrally located tumors as well as for subjects with lymph nodes involvement SBRT may be of limited valiance. Although the performances of our regimen were lower than the ones achieved by SBRT, our therapeutic option may offer a lower incidence of complications against a satisfactory local tumor control.
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PMID:Hypofractionated radical radiotherapy in elderly patients with medically inoperable stage I-II non-small-cell lung cancer. 1939 19

The objective of this study is to evaluate the efficacy and safety profile of the doxorubicin followed by cisplatin/docetaxel as primary chemotherapy for patients with locally advanced breast cancer (LABC). For this evaluation, 59 patients with LABC (T2-T4, N0-N2, M0) received three cycles of doxorubicin, followed by three cycles of cisplatin/docetaxel and followed by definitive surgery and locoregional radiotherapy with or without tamoxifen. The primary end point was pathologic complete response (pCR) in breast and axilla. Fifty-nine patients were evaluable for analysis: median age: 41 years, premenopausal: 68%, median tumor size: 6.0 cm (4-10), Stage IIB: 32% and IIIA/IIIB: 68%, both ER/PR positive: 53%, Her2/neu (3+) by IHC staining: 29%. Clinical complete response was seen in 44%, and clinical partial response was seen in 56%. Breast conserving surgery was performed in 44%, and MRM in 56%. pCR in the breast was 30.5%, in axilla was 37%, and pCR in both breast and axilla was 24%. Overall at follow-up of 60 months, the disease-free (DFS) and overall survival (OS) were 70 and 82%, respectively. The DFS and OS of patients who achieved complete pathologic response in breast and axilla were 78 and 100%, respectively, while 14 patients relapsed of which 46% were Her2 positive. Sequential combination of doxorubicin followed by docetaxel/cisplatin is a safe, feasible, and active combination, which offers the possibility of conservative surgery and is associated with high clinical and pathologic response rates, with promising and encouraging survival outcomes.
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PMID:Prospective phase II study of neoadjuvant doxorubicin followed by cisplatin/docetaxel in locally advanced breast cancer. 1952 2

The purpose of this study is to determine the presence of disseminated tumor cells in bone marrow or apheresis product, and also to evaluate the clinical significance of contaminated products and the efficacy of CD34(+) selection and high-dose chemotherapy in patients with Stage III breast cancer. Fifty-five patients were enrolled in this prospective cohort study. Whereas CD34(+) positive selection was not carried out in the first group (unselected group, n:31), CD34(+) positive selection was performed in the second group (CD34 selected group, n:24). Tumor cells were detected with anticytokeratin monoclonal antibody in the bone marrow, apheresis product and positive fraction. Tumor cells were found in six (19.3%) patients in unselected group and four patients (16.6%) in CD34 selected group (P = 0.76). The percentages of distant metastases were found higher in unselected group (51.6% vs. 25%, P < 0.01). Although there were no differences between the two groups for disease free survival (DFS; 44% vs. 74%, P = 0.24) or overall survival (54% vs. 68%, P = 0.84), DFS was significantly lower in patients with tumor cells than in patients without tumor cells (21% vs. 62%, P = 0.02). In conclusion, the presence of tumor cells in bone marrow or apheresis product decreases DFS in patients with Stage III breast cancer who underwent high-dose chemotherapy. CD34(+) selection does not change survivals, but it may decrease the distant metastases.
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PMID:The clinical significance of tumor cells in bone marrow or apheresis product and the efficacy of CD34+ selection and high-dose chemotherapy in patients with Stage III breast cancer. 1981 61

The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.
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PMID:Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors. 1982 89

Hepatectomy is accepted as the standard therapy in patients with resectable liver metastases. In recent years, the techniques such as microwave coagulation therapy (MCT) and radiofrequency ablation therapy (RFA) have been developed, so we have many options to treat. We evaluated nineteen subjects with cases of liver metastases who underwent thermoablative procedures with or without hepatectomy. RFA and MCT were used in 6 cases and 2 cases, respectively. In other 11 cases, they received a combined therapy: RFA+hepatectomy in 5 cases, and MCT+hepatectomy in 6 cases. Thermoablative therapy was used for 39 metastatic tumors. The mean tumor size was 13.7 mm, and a local recurrence was observed in 8 nodules (21%). No significant differences were observed in DFS and OS between thermoablative therapy and hepatectomy. Many patients with liver metastases received a repeated treatment, so we have to care about the remnant liver function. We conclude that thermoablative therapy with hepatectomy seems to be a less invasive procedure and effective therapy.
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PMID:[Evaluation of local coagulation therapy with hepatectomy for liver metastases]. 2003 17

We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.
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PMID:Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias. 2004 95

Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, 'progression' of AFP was defined by >15 microg/L per month before LT. A total of 127 (83%) were transplanted under and 26 (16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP>15 microg/L per month and preoperative nodules>3 were associated with decreased OS. Progression group and age>60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor>30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP>15 microg/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness.
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PMID:Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. 1995 Dec 78

An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis.
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PMID:Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients. 2036 86


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