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Positive Tumors (positive + tumor)
Terms modified by Positive Tumors Selected AbstractsThymidylate synthase polymorphisms and colon cancer: Associations with tumor stage, tumor characteristics and survivalINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Karen Curtin Abstract Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. We investigated the role of functional polymorphisms in the TS 5,-UTR promoter enhancer region (TSER, 3 or 2 repeats of a 28-bp sequence) and the 3,-UTR (1494delTTAAAG) and their association with colon tumor characteristics, including tumor stage and acquired mutations in p53, Ki- ras and microsatellite instability. Data from a population-based incident case,control colon cancer study in northern California, Utah and Minnesota (1,206 cases, 1,962 controls) was analyzed using unordered polytomous logistic regression models. In both men and women, individuals with variant TS alleles were at reduced risk of having an advanced stage tumor (metastatic disease: OR = 0.35, 95% CI: 0.2,0.6 vs. wildtype TSER and 3,-UTR). Stage-adjusted survival did not differ by genotype. Men with 1 or 2 variant alleles in both the TSER and 3,-UTR genotypes had a 50% reduced risk of a p53 -positive tumor (OR = 0.5, 95% CI: 0.3,0.9 vs. homozygous wildtype TSER and 3,-UTR). Women with 1 or 2 variant alleles for either the TSER or 3,-UTR polymorphism had reduced risk of having any colon tumor that did not vary by mutation status. This study provides some support for associations between TS genotype and colon cancer tumor characteristics. © 2007 Wiley-Liss, Inc. [source] Targeted therapy of renal cell carcinoma: Synergistic activity of cG250-TNF and IFNgINTERNATIONAL JOURNAL OF CANCER, Issue 1 2009Stefan Bauer Abstract Immunotherapeutic targeting of G250/Carbonic anhydrase IX (CA-IX) represents a promising strategy for treatment of renal cell carcinoma (RCC). The well characterized human-mouse chimeric G250 (cG250) antibody has been shown in human studies to specifically enrich in CA-IX positive tumors and was chosen as a carrier for site specific delivery of TNF in form of our IgG-TNF-fusion protein (cG250-TNF) to RCC xenografts. Genetically engineered TNF constructs were designed as CH2/CH3 truncated cG250-TNF fusion proteins and eucariotic expression was optimized under serum-free conditions. In-vitro characterization of cG250-TNF comprised biochemical analysis and bioactivity assays, alone and in combination with Interferon-, (IFN,). Biodistribution data on radiolabeled [125J] cG250-TNF and antitumor activity of cG250-TNF, alone and in combination with IFN,, were measured on RCC xenografts in BALB/c nu/nu mice. Combined administration of cG250-TNF and IFN, caused synergistic biological effects that represent key mechanisms displaying antitumor responses. Biodistribution studies demonstrated specific accumulation and retention of cG250-TNF at CA-IX-positive RCC resulting in growth inhibition of RCC and improved progression free survival and overall survival. Antitumor activity induced by targeted TNF-based constructs could be enhanced by coadministration of low doses of nontargeted IFN, without significant increase in side effects. Administration of cG250-TNF and IFN, resulted in significant synergistic tumoricidal activity. Considering the poor outcome of renal cancer patients with advanced disease, cG250-TNF-based immunotherapeutic approaches warrant clinical evaluation. © 2009 UICC [source] Her-2/neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab-based therapy in patients with metastatic breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 5 2006Gernot Hudelist Abstract Her-2/neu overexpression in human breast cancer leads to an aggressive biological behavior and poor prognosis. Although the anti-Her-2/neu antibody trastuzumab (Herceptin®) has become a valuable therapeutic option for patients with Her-2/neu -overexpressing breast cancer, many patients do not benefit from this therapy. To evaluate the effect of receptor activation on tumor response, we have investigated the phosphorylation status of Her-2/neu and EGFR in 46 Her-2/neu -overexpressing tumor samples from trastuzumab-treated metastatic breast cancer patients by immunohistochemistry. Activated (p)tyr-1248 Her-2/neu was detected in 9 of 46 breast cancers (20%), and activated (p)tyr-845 and (p)tyr-1173 EGFR were both present in 6 tumors (13%) while EGFR was present in 16 cases (35%). ptyr-1248 Her-2/neu showed a trend to correlate with increased response to trastuzumab (p = 0.063), while ptyr-845, ptyr-1173 EGFR and EGFR did not. The presence of ptyr-1248 Her-2/neu and ptyr-845 or ptyr-1173 EGFR, however, was a strong predictor of both response to trastuzumab-based treatment (OR = 8.0, p = 0.021 and OR = 8.0, p = 0.021) and clinical benefit (OR = 5.47, p = 0.041 and OR = 6.22, p = 0.028 multivariate logistic regression analysis). Furthermore, ptyr-845 EGFR and ptyr-1248 Her-2/neu were both independent predictors of progression-free survival (RR = 0.21, p = 0.01 and RR = 0.45, p = 0.026, multivariate analysis). Patients with ptyr-845 EGFR positive tumors also tended toward increased overall survival (RR = 0.17, p = 0.082). Taken together, we have demonstrated that the determination of activated EGFR improves the utility of ptyr-1248 Her-2/neu staining in predicting the clinical outcome of patients undergoing trastuzumab treatment. We hypothesize that the activation state of both Her-2/neu and EGFR are key determinants for trastuzumab efficacy. © 2005 Wiley-Liss, Inc. [source] Morphological and immunohistochemical characteristics of atypical fibroxanthoma with a special emphasis on potential diagnostic pitfalls: a reviewJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2010tjan Luzar The present manuscript gives emphasis on recognizing different morphological variants of atypical fibroxanthoma (AFX), on validation of immunohistochemical markers and on discussing potential diagnostic pitfalls. Material and methods: Histological features analyzed in 66 AFXs were: ulceration, morphological variants, growth pattern, location in the skin and vascular/perineural invasion. The antibodies used were CK-MNF116, CK-AE1/AE3, S100, smooth muscle actin, desmin, CD31 and EMA. Results: The study included 59 males, 7 females, aged 55,95 years, mean 77 years. All developed on sun damaged skin. Ulceration was present in 50%. Morphological patterns were pleomorphic spindle and epithelioid cells (60.6%), predominantly spindle cells (19.7%), purely spindle-cells (13.6%), and predominantly epithelioid cells (6.1%). Most were localized in the dermis (57.6%). An expansile (36.4%) rather than infiltrative (6.1%) growth into superficial subcutis was also noted. No vascular/perineural invasion was seen. Additional changes were hemorrhagic and pseudoangiomatous areas (24.2%), granular cell change (22.7%), keloid-like areas (9.1%), myxoid change (7.6%), osteoclast-like giant cells (6.1%) and clear cell change (4.6%). AFXs were consistently negative for S100, CK-MNF116, CK-AE1/AE3 and desmin. Focal positivity for SMA (45.2%), EMA (24.4%) and CD 31 (9.5%) was seen. Conclusions: A diagnosis of AFX is still made by exclusion of other malignant neoplasms with similar morphology. Immunohistochemistry plays a crucial role in this distinction, but can also be misleading. This study expands the spectrum of non-vascular CD31 positive tumors. Luzar B, Calonje E. Morphological and immunohistochemical characteristics of atypical fibroxanthoma with a special emphasis on potential diagnostic pitfalls. [source] BS12 PREDICTIVE MARKERS FOR BREAST CANCER NEOADJUVANT CHEMOTHERAPYANZ JOURNAL OF SURGERY, Issue 2007S. Syed Purpose Although neoadjuvant chemotherapy (NACT) is routinely used in the management of breast cancer, there is no definitive way of predicting which patients are more likely to respond to a particular therapy. The aim of this study was to identify markers that can be used to predict tumor response to chemotherapy in breast cancer. Methodology We used immunohistochemistry to evaluate blood microvessel density (MVD) (CD31), tumor cell proliferation (Ki-67), anti-apoptotic marker (Bcl-2), ER and PR expression, and HER-2/neu expression in core biopsy samples (taken before chemotherapy) from patients with locally advanced breast cancer (n = 20), receiving neo-adjuvant chemotherapy {anthracycline-based regimen (FEC100) (n = 10) vs single agent taxane regimen (docetaxel) (n = 10), and correlated these factors with tumor response (as assessed clinically and by tumor imaging) after 4 cycles of treatment. Results Tumors expressing low levels of Bcl-2 showed significantly greater reduction in size to both taxane (P < 0.05) and anthracycline-based (P < 0.01) regimens, compared to tumors expressing high levels of Bcl-2. Further, HER-2/neu positive tumors showed significantly greater reduction in size to taxane regimen (P < 0.05), while estrogen receptor (ER) negative tumors showed a trend of greater reduction in size to anthracycline-based regimen (P = 0.06). Conclusions Bcl-2 and HER-2/neu expression may be useful markers to predict response to neoadjuvant chemotherapy in breast cancer. While subject numbers are still too low to draw firm conclusions, the current data indicates that HER-2/neu may specifically predict a positive tumor response to taxane regimen, and high Bcl-2 is a marker of chemoresistance. [source] HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinomaCANCER, Issue 11 2005Peter A. Learn M.D. Abstract BACKGROUND The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a , 50% regression in clinical tumor size prior to surgery. RESULTS In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu -negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2,13.0) in favor of docetaxel. Women who had HER-2/neu -negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu -positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu -negative tumors to match that observed in women who have HER-2/neu -positive tumors treated with AC alone. Cancer 2005. © 2005 American Cancer Society. [source] Lack of association between amplification of her-2 and response to preoperative taxanes in patients with breast carcinomaCANCER, Issue 2 2004Ana M. Gonzalez-Angulo M.D. Abstract BACKGROUND The objective of the current study was to determine whether her-2 amplification was associated with a pathologic response to preoperative chemotherapy with taxanes in patients with early-stage breast carcinoma. METHODS The authors evaluated 71 patients treated for AJCC Stage II and III breast carcinoma with preoperative taxanes whose tissue specimens were still available. Fifty-seven patients (80%) had received paclitaxel and 14 (20%) had received docetaxel (4 cycles of either drug). Amplification of the her-2 gene was determined using fluorescence in situ hybridization. RESULTS The median patient age was 49 years (range, 21,70 years). Forty-eight patients (68%) had Stage II breast carcinoma and 23 (32%) had Stage III disease. her-2 gene amplification was detected in 19 tumor specimens (28%). Hormone receptors (estrogen and/or progesterone) were detected in 11 her-2,positive tumor specimens (58%) and in 31 her-2,negative tumor specimens (85%). Eight pathologic complete responses (pCR; breast and axillary lymph nodes) occurred, 3 (16%) in patients with her-2,positive tumor specimens and five (10%) in patients with her-2,negative tumor specimens (P = 0.68). Twelve patients achieved pCR in the breast, 5 (26%) in patients with her-2,positive tumors and 7 (15%) in patients with her-2,negative tumors (P = 0.3). At a median follow-up of 61 months, none of the patients with a pCR developed recurrent disease, regardless of their her-2 status. The progression-free and overall survival rates were similar in both HER-2,positive and her-2,negative groups (P = 0.45 and P = 0.14, respectively). CONCLUSIONS her-2 gene amplification was not found to be predictive of a pathologic response to preoperative taxanes in patients with early-stage breast carcinoma. Cancer 2004. © 2004 American Cancer Society. [source] Is breast cancer survival improving?CANCER, Issue 1 2004Trends in survival for patients with recurrent breast cancer diagnosed from 1974 through 2000 Abstract BACKGROUND Despite advances in therapies for breast cancer, improvement in survival for patients with recurrent or metastatic breast cancer has been difficult to establish. The objective of the current study was to determine whether the survival of women with recurrent breast cancer has improved from 1974 to 2000. METHODS The authors analyzed the survival experience of 834 women who developed recurrent breast cancer between November 1974 and December 2000. All patients had been treated previously with adjuvant anthracycline-based protocols. Patients were divided into five consecutive groups based on year of breast cancer recurrence, and survival was compared across the five groups. Because some prognostic variables were divided unevenly divided among the cohorts, a multivariate model was created to determine the association of year of recurrence and survival after accounting for other prognostic factors. RESULTS In the unadjusted analysis, there was a statistically significant improvement in survival across the five groups, and the more recent cohorts had longer survival (P < 0.001). Other variables that predicted longer survival after breast cancer recurrence included smaller initial tumor size, lower stage of disease, fewer lymph nodes involved, longer disease-free interval, estrogen receptor,positive tumors, and nonvisceral dominant site of disease recurrence. In the multivariate analysis, which adjusted for these prognostic factors, year of recurrence was associated with a trend toward improved survival, with a 1% reduction in risk for each increasing year. CONCLUSIONS For these cohorts of patients, the authors present data suggesting that the prognosis for patients with recurrent breast cancer improved between 1974 and 2000. Cancer 2004;100:44,52. © 2003 American Cancer Society. [source] Dynamic alterations of the extracellular environment of ovarian surface epithelial cells in premalignant transformation, tumorigenicity, and metastasisCANCER, Issue 8 2002Callinice D. Capo-Chichi Ph.D. Abstract BACKGROUND Ovarian surface epithelial cells are positionally organized as a single cell layer by a sheet of basement membrane. It is believed that the contact of the ovarian surface epithelial cells with the basement membrane regulates cell growth and ensures the organization of the epithelium. Disabled-2 (Dab2), a signal transduction protein and a candidate tumor suppressor of ovarian carcinoma, functions in positional organization of ovarian surface epithelial cells. In ovarian carcinomas, genetic and epigenetic changes enable the tumor cells to escape positional control and proliferate in a disorganized fashion. Alterations in the extracellular environment may also be critical for tumor initiation and progression. METHODS We analyzed and compared the presence of collagen IV and laminin, the scaffold proteins of the basement membrane, and Dab2 in 50 ovarian tumors that are restricted to the ovaries and in 50 metastases of ovarian tumors by immunohistochemistry. Expression of collagen IV, laminin, and Dab2 was also analyzed by Northern blotting in a panel of human ovarian surface epithelial and cancer cell lines. RESULTS The basement membrane is often absent in morphologically benign ovarian surface and cyst epithelium and low-grade tumors and collagen IV and laminin are absent in the extracellular matrix of most of the primary tumors tested. Of the 50 ovarian tumors confined to the ovaries, 6% (3 of 50) were collagen IV positive and 24% (12 of 50) were laminin positive tumors. Of the 50 metastatic tumors, 16% (8 of 50) are collagen IV positive and 86% (43 of 50) are laminin positive. In addition, even in the metastatic ovarian tumors that are largely collagen IV negative, there are pockets of local areas in which the tumor cells are surrounded by collagen IV-positive staining. Dab2 is absent in the majority of ovarian tumors found in both ovaries and metastatic sites. In both nontumorigenic human ovarian surface epithelial and cancer cell lines, collagen IV, laminin, and Dab2 are expressed aberrantly. CONCLUSIONS Loss of the basement membrane may be an early event in the preneoplastic transformation of ovarian surface epithelium and in the early stages of tumorigenesis before tumor invasion and metastasis. The majority of primary ovarian tumors examined lack collagen IV and laminin in their extracellular matrix. However, expression of laminin is restored in the majority of metastatic tumors. Reexpression of collagen IV may also contribute to tumor metastasis. The ability of tumor cells to dynamically alter the expression of collagen IV and laminin may facilitate the shedding of cancer cells into the peritoneal spaces and subsequent attachment to the metastatic sites. We propose that loss of collagen IV and laminin may be an initial event in ovarian tumorigenicity and that restoration of collagen IV and laminin expression in the later stages of tumor development may promote metastasis of ovarian tumors. Cancer 2002;95:1802,15. © 2002 American Cancer Society. DOI 10.1002/cncr.10870 [source] HER-2/neu overexpression in patients with radically resected nonsmall cell lung carcinomaCANCER, Issue 10 2002Impact on long-term survival Abstract BACKGROUND Using immunohistochemistry, the authors prospectively investigated the expression of HER-2/neu protein in radically resected specimens of nonsmall cell lung carcinoma (NSCLC) and evaluated its impact on long-term prognosis. METHODS Between January 1991 and February 1992, surgical specimens from 130 consecutive patients who underwent radical resection for NSCLC (60 squamous cell carcinoma, 48 adenocarcinoma cases, and 22 large cell carcinomas) and that were staged (according to the TNM staging system) pathologically as Stage I (41 cases [ 32%]), Stage II (37 cases [28%]), and Stage IIIA (52 cases [40%]) were investigated for the expression of HER-2/neu using an avidin-biotin complex immunohistochemical technique. A semiquantitative four-stage grading system was used (0%, 1,5%, 6,20%, and > 20% positive cells) and an average number of 1500 cells/section was considered. Data were correlated with clinical and pathologic variables. RESULTS Normal bronchial tissue was found to be completely negative for HER-2/ neu expression whereas 21 of the 130 tumor specimens (16%) were positive (range 1,> 20%). HER-2/neu positivity did not appear to differ significantly among pathologic stages and histotypes. Using a predetermined cutoff value of 5% positive cells, 15 tumor specimens (12%) were found to be above this value. The median survival time (85 weeks vs. 179 weeks) and overall survival rate were significantly lower in patients with > 5% HER-2/neu -positive tumors (hazard ratio for the group with > 5% positive cells: 2.94, 95% confidence interval, 1.62,5.34; P < 0.0004). On multivariate analysis, HER-2/ neu and extent of tumor emerged as independent factors for disease-related mortality. CONCLUSIONS In NSCLC, the negative impact of HER-2/neu overexpression on survival was maintained in the long-term follow-up of radically resected patients. HER-2/neu overexpression may be a valuable prognostic factor as well as a potential target for biologic therapies. Cancer 2002;94:2669,74. © 2002 American Cancer Society. DOI 10.1002/cncr.10531 [source] Monoclonal antibodies to target epidermal growth factor receptor,positive tumorsCANCER, Issue 5 2002A new paradigm for cancer therapy Abstract BACKGROUND Traditional cytotoxic approaches to tumor management are associated with efficacy and toxicity limitations. Blockade of the epidermal growth factor receptor (EGFR) and its ligands is a novel approach to the treatment of human tumors that offers a noncytotoxic alternative to cancer treatment. METHODS An English-language literature search was conducted to identify studies assessing the in vitro and in vivo effects of EGFR blockade with an emphasis on approaches that use monoclonal antibody therapy. RESULTS The EGF pathway regulates normal cellular processes and appears to be correlated with the development of malignancy. Approximately 30% of human tumors express EGFR, which has been reported to be correlated with poor prognosis and diminished disease-free and overall survival in selected tumor types. A number of anti-EGFR monoclonal antibodies have been developed, which currently are undergoing clinical trials in humans. Effective anti-EGFR monoclonal antibodies compete with endogenous ligands, primarily EGF and transforming growth factor,,, for receptor ligand-binding sites. Binding to EGFR blocks critical signaling pathways and interferes with the growth of tumors expressing EGFR. Anti-EGFR monoclonal antibodies that currently are under study include IMC-C225, EMD 55900, ICR 62, and ABX-EGF. CONCLUSIONS These antibodies have demonstrated promising results and appear to have been well tolerated. EGFR-targeted therapy addresses important, unmet needs in the treatment of human tumors, particularly EGFR-positive epithelial tumors including common malignancies of the head and neck, lung, and colon. Cancer 2002;94:1593,611. © 2002 American Cancer Society. DOI 10.1002/cncr.10372 [source] | ||||||||||