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)

The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for non-responders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer. Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy.
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PMID:Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. 1131 80

Our objective was to investigate the prognostic significance of cell turnover (apoptosis and proliferation) in breast cancer patients. Apoptosis was microscopically quantitated on histological sections from 791 breast cancer patients with long-term follow-up (median, 16.3 years). Apoptotic counts were also compared with proliferation data (mitotic counts and MIB-1 labeling); apoptosis data derived from terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay; and pathobiological variables, including p53, erbB-2, and estrogen receptor (ER). High apoptotic counts were associated with increased cellular proliferation, ER negativity, immunopositivity of erbB-2 and p53 (P < 0.0001), and shortened disease-specific survival (DSS; P = 0.0009) and disease-free survival (DFS; P = 0.0006). Other factors associated with shortened DFS and DSS by univariate analysis were high tumor grade, nodal metastases, and large tumor size (P < 0.0001 for each). Multivariate analysis of data for all of the patients demonstrated that tumor size, nodal status, ER, histological grade, and erbB-2 showed independent prognostic value. In node-negative patients, tumor size and mitotic rate per 1000 cells independently predicted DFS (P = 0.0055). Tumor grade was the only independent predictor of DSS. For node-positive patients, tumor size, nodal status, ER, and erbB-2 were independent prognostic factors. The number of mitoses per 1000 was independently associated with DFS (P = 0.043) but not with DSS. Apoptosis data did not provide independent prognostic value in any, node-positive or node-negative, breast cancer patients.
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PMID:Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. 1141 May 11

On fresh frozen tumor tissue from 161 patients with endometrial cancer DNA-ploidy and S-phase fraction were measured in a prospective study to evaluate their prognostic and predictive value. All FIGO stage I or II patients had surgery and were included in an adjuvant trial comparing tamoxifen 30 mg p.o. versus medroxyprogesterone acetate 500 mg p.o. for 2 years versus no therapy. Diploid (DNA index (DI) </= 1.1) tumors were found in 75%. S-phase fraction was elevated (>5%) in 46 (30%) of the patients. Significant correlations of DNA-ploidy and S-phase fraction were found with classical parameters such as stage, grade, histologic type and estrogen and progesterone receptor status. Patients with FIGO stage I aneuploid tumors showed significantly shorter disease-free interval (DFS) and overall survival (OAS). Recurrences and deaths occurred more often in tumors with raised S-phase fraction. In these early stages clinical outcome was worst if both factors were unfavorable. In multivariate analysis of stage I tumors DNA-ploidy and S-phase fraction were independent of grade, type and estrogen receptor status. Patients whose tumors had elevated S-phase fractions (>5%) gained more benefit from endocrine treatment than patients with low S-phase fractions. Patients with diploid and aneuploid tumors had prolonged DFS and improved OAS, if they had received adjuvant hormonal therapy. In endometrial cancer, DNA-ploidy and S-phase fraction are objective and reliable prognostic and predictive parameters which should be integrated into the clinical management.
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PMID:Prognostic importance of DNA-ploidy and S-phase fraction in endometrial cancer. 1157 14

Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell depletion should be restricted to the CD4 subset.
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PMID:Autologous peripheral blood stem cell transplantation in tumor-stage mycosis fungoides: predictors of disease-free survival. 1159 68

Tumor angiogenesis is believed to be related to prognostic factors involved in tumor development and metastasis. Using immunohistochemical methods, we evaluated tumor angiogenesis in 42 early invasive breast cancer patients (T1-2, NO-1-2, M0). Four patients received tamoxifen, 25 patients received CAF or CA, and 15 patients received CMF as adjuvant therapy. The median follow-up was 47 (range 24-119) months. Ten patients (43.5%) in the node-positive group and 2 patients (10.5%) in the node-negative group relapsed (p = 0.019). The mean microvessel count (MVC) was 60.3 3.05 per 200x field (range: 16-95). MVCs of postmenopausal and premenopausal patients were 50.13 +/- 5.74 and 68.64 +/- 4.11, respectively, in the axillary lymph node (ALN)-negative patient group (p = 0.04). Staining was moderate to strong in 13 (68%) ALN-negative and in 17 (74%) ALN-positive patients (p > 0.05), and was also moderate to strong in 82% of premenopausal patients and in 50% of postmenopausal patients (p = 0.037). There was no significant relationship between angiogenesis and p53, nor was angiogenesis significantly associated with the patient ER status and tumor size. No significant correlations were found between OS/DFS and Factor VIII staining or p53 (log rank test, p > 0.05). Of all ALN-negative patients with increased angiogenesis, one patient of the CMF group relapsed, but no recurrence occurred in patients undergoing anthracycline-based chemotherapy (p > 0.05). On the other hand, of all ALN-positive patients with increased angiogenesis, 5/14 patients treated with anthracylcine and 2/2 CMF-treated patients relapsed (p = 0.175). Despite the statistical insignificance, anthracycline-based adjuvant chemotherapy appears to be more effective than CMF as regards relapse prevention particularly in early ALN-positive breast cancer patients with increased angiogenesis. Additional studies are necessary to demonstrate the clinical importance of angiogenesis.
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PMID:Prognostic importance of tumor angiogenesis in breast carcinoma with adjuvant chemotherapy. 1186 15

NST is becoming a widely accepted method for allogeneic HSCT. Much experience has been gained, and the biology, indications and limitations are becoming clearer. Nonmyeloablative conditioning allows consistent engraftment of allografts from matched related, unrelated, and even partially matched donors. NST has been able to reduce the toxicity of allogeneic HSCT. The better immediate outcome produces better overall DFS. NST was feasible in elderly patients with almost no upper age limit, and in patients with organ dysfunction or other comorbidities precluding standard ablative conditioning. NST has also reduced the regimen-related toxicity of allogeneic HSCT in high-risk setting such as HSCT in heavily pretreated patients or following failure of a prior transplant procedure and in the unrelated setting. NST is rapidly becoming the treatment of choice in these indications where toxicity of standard ablative therapy is unacceptable. In certain malignancies such as in NHL, Hodgkin's disease and multiple myeloma, standard ablative NST has been reported to result in exceptionally high treatment related mortality, and NST is being investigated as a more reasonable alternative. NST may reduce the toxicity of the procedure even in younger patients who are eligible for ablative HSCT as well, however the long-term impact on patient outcome in this group is not yet established, and NST merits further investigation in prospective comparative trials. As described above, the known susceptibility of the underlying malignancy to GVT, the response to prior chemotherapy and bulk of residual disease, and the type of donor are other factors to consider when considering NST, and when selecting a regimen. The optimal preparative regimen needs to be defined. Ultimately less chemotherapy will be used and more specific immune-modulation, rather than intense nonspecific immunosuppression, will be used to achieve HVG tolerance. Preliminary animal models using costimulation blockade for specific induction of tolerance are promising steps towards achievement of this goal. Although much progress has been achieved with consistent achievement of engraftment with NST, GVHD and disease recurrence remain major obstacles to successful treatment. Existing clinical data suggest that NST does limit the incidence and severity of GVHD. Limitation of regimen-related toxicity, and bilateral transplantation tolerance afforded by mixed chimerism, are believed to have a major role in limiting GVHD. However GVHD remains the primary cause of treatment-related mortality. The development of techniques to separate GVHD and GVL are essential for further improvement of NST outcome. Better understanding of the biology and targets of GVHD and GVL may allow the elimination of alloreactive T-cells responsible for GVHD from the graft while retaining T-cells with GVL and infection control potential. Recurrence of the underlying malignancy is a major complication when NST is attempted in patients with chemo-refractory diseases and with high tumor bulk. Reduced toxicity regimens such as the FB/ATG regimen have been somewhat more successful in controlling disease progression until a potent GVT effect is established. However novel approaches are urgently required. NST serves as a platform for cellular immunotherapy. Judicious use of pre-emptive DLI needs to be explored. DLI may be amplified by activation of donor lymphocytes with IL-2 or in vivo administration of IL-2. Identification of tumor antigens will lead the way to ex-vivo generation and expansion of tumor specific cytotoxic T-lymphocytes to be used as potent immunotherapy without the hazards of GVHD. Allogeneic transplantation is rapidly changing from administration of supralethal doses of chemotherapy and radiation, trying to physically eliminate the 'last tumor cell', to the more subtle and tolerated sophisticated immunotherapy. This effort will focus on specific induction of HVG tolerance followed by induction of tumor-specific GVT effect to cure the underlying malignancy.
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PMID:Non-myeloablative hematopoietic stem cell transplantation (NST) in the treatment of human malignancies: from animal models to clinical practice. 1190 95

To assess the frequency and prognostic impact of Ep-CAM and Her-2/neu overexpression in patients with breast cancer and to determine its relationship with other prognostic markers, 205 breast cancer patients with a median follow-up of 10.8 years were enrolled in this retrospective study. Overexpression of Ep-CAM and Her-2/neu in tumor tissue samples was assessed by immunohistochemistry. Tumors presenting a Her-2/neu 2+ staining were additionally analyzed by FISH to exclude false positive results. Ep-CAM and Her-2/neu overexpression was found in 35.6% and 19.5% of the tumor samples, respectively. Both Ep-CAM and Her-2/neu overexpression were predictive for poor disease-free (DFS) and disease-related overall survival (DROS). Concurrent Ep-CAM and Her-2/neu overexpression was present in 13.2% of tumor specimens and had an additive negative impact on DFS and DROS. This minority of patients had a median time to relapse of only 34 months, whereas the median time to relapse was not reached in the patient population without Her-2/neu and Ep-CAM overexpression. By multivariate analysis Ep-CAM overexpression proved to be an indicator of poor prognosis, independent of tumor size, histologic grade, hormone receptor expression and Her-2/neu overexpression. In conclusion, overexpression of Ep-CAM and Her-2/neu complement each other as predictors for poor prognosis in patients with invasive breast cancer. Determination of these tumor markers should help in assigning breast cancer patients to 1 of 3 distinct risk categories.
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PMID:Prognostic significance of Ep-CAM AND Her-2/neu overexpression in invasive breast cancer. 1194 67

Soluble and nuclear estrogen receptor (ER) content was measured by ligand binding assay, and estrogen and progesterone receptors by immunohistochemical assays (ER-ICA and PR-ICA) in 214 patients with breast cancer recruited at the "M. Ascoli" Cancer Hospital Centre in Palermo, Sicily, to assess the discriminant and predictive value of these parameters. On follow-up, data from both ER-ICA and PR-ICA showed a statistically significant difference, PR-positive patients having longer disease-free (DSF) and overall (OS) survival than PR-negative ones. Conversely, ER status did not correlate significantly with both DFS (P = 0.6) and OS (P = 0.2). In particular, PR-positive patients had 59 +/- 18 months DFS and 67 +/- 12 months OS, compared to 51 +/- 22 months DFS and 57 +/- 17 months OS of PR-negative cases. The present evidence implies that a PR-negative status identifies breast cancer patients with early relapse, as also suggested by previous studies. It also agrees with the results of ligand binding assay of ER, where ER status is a good discriminant and predictor of response to endocrine treatment, but is unable to anticipate early relapse in breast cancer patients. Evidence that PR status is a statistically significant prognostic indicator deserves further study to ascertain whether or not PR should be regarded as an ER-dependent parameter or be related to other biological variables such as growth factor (e.g., EGF), oncogene (e.g., Her2/Neu), or tumor suppressor gene (e.g., p53) products.
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PMID:Ligand binding and cytochemical analysis of estrogen and progesterone receptors in relation to follow-up in patients with breast cancer. 1209 34

Our purpose was to determine the predictive value of tumor biologic parameters in patients with HRPBC who received HDCT with ASCT as first-line treatment. From September 1992 to May 2000, 149 stage II or III HRPBC patients were enrolled in a single-arm trial using a tandem HDCT regimen followed by ASCT. Her2/neu, p53, Ki67 and bcl-2 protein expression was studied using immunohistochemic staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA index) and tumor cell proliferation (SPF) were measured by DNA flow cytometry. The relationship between these tumor biologic parameters, on the one hand, and DFS, DDFS and OS, on the other, was analyzed. With a median follow-up of 43 months (range 7-106), p53 protein accumulation (p = 0.000004), negative combined hormone receptor status (p = 0.003) and Her2/neu overexpression (p = 0.02) were significant negative predictors of OS in univariate analysis. A poorer DFS was associated with p53 positivity (p = 0.04) and nodal ratio > or = 0.8 (p = 0.008). Poorer DDFS was associated with p53 positivity (p = 0.03). In multivariate analysis, Her2/neu overexpression (RR = 3.86, 95% CI 1.48-10.1, p = 0.006) and p53 overexpression (RR = 6.06, 95% CI 2.22-16.52, p < 0.001) proved to be independent predictors of adverse OS. p53 overexpression was the only independent predictor of DFS (RR = 2.21, 95% CI 1.07-4.57, p = 0.03). p53 overexpression and Her2/neu overexpression are independent negative predictors of survival in HRPBC treated with HDCT. The adverse impact of these biologic features was probably not altered by HDCT. For HRPBC patients with tumors not overexpressing Her2/neu or p53, HDCT may be an appropriate approach to achieve long-term survival and tumor control.
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PMID:P53 is the strongest predictor of survival in high-risk primary breast cancer patients undergoing high-dose chemotherapy with autologous blood stem cell support. 1211 43

Adjuvant chemotherapy reduces the incidence of distant metastasis and increases survival of patients with colorectal cancer. However, predictive markers are needed to define subsets of patients with stage II and III disease that may benefit from adjuvant treatment. A secreted member of the TNF receptor superfamily, the decoy receptor 3 (DcR3), was reported to be amplified in colorectal cancer as a negative regulator of Fas-mediated apoptosis. We analyzed DcR3 gene copy number and protein expression in a large series of tumors from a randomized multicenter trial of 5-fluorouracil/mitomycin C (FU/MMC) adjuvant chemotherapy of the Swiss Group for Clinical Cancer Research (SAKK 40/81), using real-time quantitative PCR and immunohistochemistry on tumor microarrays. Results of gene status and protein expression of DcR3 were correlated with disease-free and overall survival of patients. We observed amplification of the DcR3 gene in 185/294 (63%) and overexpression of the DcR3 protein in 163/223 (73%) of colorectal tumors. Multivariate analysis showed no prognostic effect of DcR3 gene amplification and protein overexpression. However, adjuvant chemotherapy was significantly more beneficial in patients with normal DcR3 gene copy number than in patients with amplification (DFS: HR 2.84, 95% CI 1.16-6.98, p = 0.02; OS: HR 3.15, 95% CI 1.19-8.32, p = 0.02), whereas DcR3 protein overexpression did not influence the effect of adjuvant chemotherapy (DFS: HR 1.02, 95% CI 0.65-1.60, p = 0.95; OS: HR 0.95, 95% CI 0.61-1.49, p = 0.83). We conclude that amplification of the 20q13 locus is a predictive marker for adjuvant chemotherapy in colorectal cancer.
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PMID:DCR3 locus is a predictive marker for 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer. 1239 45


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