| Targeted inhibition of mammalian target of rapamycin for the treatment of advanced renal cell carcinoma
May 28, 2009 at 6:51 am
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| | Clinical trials have validated the importance of mammalian target of rapamycin (mTOR) as a targeted mechanism in the treatment of renal cell carcinoma (RCC). Temsirolimus, an mTOR inhibitor that is approved for treatment of advanced RCC, has demonstrated both overall survival benefits and progression-free survival benefits versus interferon-[alpha] as first-line treatment for patients with poor prognostic features. Exploratory subset analyses indicated that temsirolimus benefits patients with RCC regardless of tumor histology or nephrectomy status. Everolimus, the second mTOR inhibitor to demonstrate activity in RCC, improved progression-free survival versus placebo in patients whose disease progressed after treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors (sunitinib, sorafenib, or both); benefit was observed for all risk groups. Deforolimus also exhibited antitumor activity against RCC in early clinical studies. There is now compelling clinical evidence for the effectiveness of targeting mTOR in the treatment of RCC. Cancer 2009. © 2009 American Cancer Society. |
| Macroscopic assessment of mesorectal excision in rectal cancer
May 28, 2009 at 6:50 am
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| | High quality of surgical technique and the use of descriptive measures to assess and report surgical proficiency have been shown to influence locoregional tumor control in patients with rectal cancer. In this study, the authors have aimed to audit the implementation of a macroscopic assessment of mesorectal excision (MAME) and to investigate factors that influenced surgical quality and disease recurrence.All curative resections for rectal cancer were prospectively evaluated for MAME between 1998 and 2007. Mesorectal specimens were graded into 3 types: complete, nearly complete, and incomplete categories. Univariate and multivariate analyses identified independent risk factors for noncomplete mesorectum categories as well as local and overall tumor recurrence.Of 359 specimens, 294 (81.9%) underwent evaluation; 82.3% were "complete." Abdominoperineal resection (APR) was the sole covariate associated with inadequate mesorectal excision (odds ratio [OR] = 2.7; P = .003). Independent predictors of local recurrence were circumferential resection margin (CRM) involvement (OR = 3.6; P = .027) and noncomplete mesorectum (OR = 4.4; P = .008). CRM+ (OR = 3.1; P = .004), poorly differentiated tumors (OR = 14.2; P = .010), nodal involvement (OR = 2.9; P = .010), and APR (OR = 2.9; P = .006) were independent risk factors for overall recurrence. In lower third tumors, noncomplete mesorectum occurred more frequently in APR compared with sphincter-saving procedures (31.1% vs 18.8%; P = .088).This study demonstrates the value of auditing MAME. Good proficiency of mesorectal excision is associated with lower tumor recurrences after curative surgery, and is a morphological tool found to be useful in clinical practice. Cancer 2009. © 2009 American Cancer Society. |
| Increased vascular endothelial growth factor expression, CD3-positive cell infiltration, and oxidative stress in premalignant lesions of the cervix
May 28, 2009 at 6:50 am
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| | Vascular endothelial growth factor (VEGF) plays an important role in cervical intraepithelial neoplasia (CIN) progression. The occurrence of leukocytes has been documented in CIN; however, their role in VEGF production remains unknown. Oxidative stress has been involved in the progression of malignant neoplasias, but to the authors' knowledge tissue oxidative stress in CIN has not been documented. The objective of the current study was to investigate the expression of VEGF, leukocyte infiltration, leukocyte VEGF expression, and nitrogen/oxygen metabolism in cervical tissues from patients with CIN.Indirect immunofluorescence was used to study the expression of VEGF and leukocyte infiltration in cervical samples from 55 patients with CIN and 7 normal controls. Superoxide anion (O2-) expression was determined by a cytochemical method, and tissue and serum nitric oxide by the Griess reaction. Human papillomavirus (HPV) DNA and HPV types were identified by the hybrid capture 2 HPV DNA test.Increased expression of VEGF was observed related to the progression of CIN. A significant increment of CD3 lymphocytes was found in CIN type 3 (CIN 3) and coexpression of CD3/VEGF and monocyte-macrophage/VEGF in CIN 2 and 3. Increased O2--positive cells were found in CIN 2 and 3; however, tissue nitrate-nitrite content remained similar to controls. The incidence of HPV infection was 16% in patients with CIN. No significant differences were observed in the values of HPV-positive or HPV-negative patients.Different factors leading to cervical neoplasia progression may be involved in the evolution of CIN, and the presence of these factors is most likely not related to the HPV infection status. Cancer 2009. © 2009 American Cancer Society. |
| Reducing inequities in cancer care
May 28, 2009 at 6:50 am
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| | No abstract. |
| Mucinous gastric carcinomas
May 28, 2009 at 6:50 am
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| | Mucinous gastric carcinoma (MGC) is characterized by substantial mucous lakes within tumors and comprises 3% of gastric carcinomas at the authors' institute.The authors analyzed the clinicopathologic characteristics, mucin gene expression profiles, microsatellite instability (MSI), and status of the human epidermal growth factor receptor 2 (HER-2) and epidermal growth factor receptor (EGFR) genes in 133 MGCs and compared them with the same variables in nonmucinous gastric carcinomas (NMGCs). In addition, the prognostic implications of clinicopathologic parameters were evaluated.Patients who had MGC had deeper invasion (P = .003), more frequent lymph node metastasis (P < .001), more advanced pathologic stage (P < .001), more frequent lymphatic invasion (P < .001), and lower disease-specific survival rates (P < .0001) than patients who had NMGC. However, a mucinous histology per se was not identified as an independent prognostic factor. Negative mucin 1, cell surface associated (MUC1) status (P < .001); positive mucin 2, oligomeric mucus/gel-forming (MUC2) status (P < .001); negative mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) status (P = .036); and negative mucin 6, oligomeric mucus/gel-forming (MUC6) status (P < .001) were more frequent in MGCs. The frequency of MSI in MGC was not significantly different from that in NMGC. MGCs had a significantly lower incidence of HER-2 protein overexpression (P = .046), HER-2 gene amplification (P = .009), and EGFR protein overexpression (P = .017) than NMGCs; and multivariate analysis identified EGFR overexpression as a factor associated with a poor prognosis (P = .047). Patients with MGC who had a predominance of signet ring cells in mucin pools had poorer disease-specific survival than patients who had MGC with predominant tubular differentiation (P = .017).The clinicopathologic and molecular characteristics of MGCs differed from those of NMGCs. Furthermore, the results indicated that EGFR overexpression and histologic subtyping by predominant tumor cell type in mucin pools may be helpful for predicting clinical outcome in patients with MGC. Cancer 2009. © 2009 American Cancer Society. | | | 
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