bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum‐resistant ovarian cancer and primary peritoneal carcinomatosis
Authors: Matei Daniela , Emerson Robert E. , Schilder Jeanne , Menning Nancy , Baldridge Lee Ann , Johnson Cynthia S. , Breen Tim , McClean John , Stephens Doyle , Whalen Charles , Sutton Gregory 
Published: July 2008

AbstractBACKGROUND.Ovarian tumors frequently express c‐Kit and/or platelet‐derived growth factor receptors (PDGFRs). Imatinib mesylate blocks the growth of ovarian cancer cells in vitro and may enhance the activity of chemotherapy. This study was conducted to determine the activity of imatinib in combination with docetaxel in patients with recurrent, platinum‐resistant epithelial ovarian cancer (EOC).METHODS.Eligible patients had recurrent, platinum‐resistant, or refractory EOC that expressed PDGFRα or c‐kit, as determined by immunohistochemistry. Imatinib mesylate at a dose of 600 mg orally once daily was administered continuously with docetaxel at a dose of 30 mg/m2 given intravenously once weekly in Weeks 1 through 4 of every 6‐week cycle. The primary endpoint was objective response rate (ORR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST).RESULTS.Thirty‐four patients were screened for PDGFRα and c‐kit expression to enroll 23 patients between December 2003 and October 2005. Four patients had c‐kit‐positive/PDGFR‐negative tumors, 11 patients had PDGFR‐positive/c‐kit‐negative tumors, and 8 patients had c‐kit‐positive/PDGFR‐positive tumors. The median patient age was 56 years (range, 33‐76 years). Patients had received a median of 3 prior treatments. The ORR was 21.7% and included 1 complete and 4 partial responses. An additional 3 patients had stable disease for more than 4months. Expression of PDGFR, c‐kit, phosphatase and tensin homolog (PTEN), and phosphorylated protein kinase B (Akt) did not predict response to therapy. The most common adverse events encountered were fatigue (83%), nausea (74%), diarrhea (61%), anorexia (52%), and edema (65%), and the majority of those events were graded as grade 1 or 2.CONCLUSIONS.The combination imatinib and docetaxel was tolerated in patients with heavily pretreated EOC that expressed c‐kit or PDGFRα. Few patients had sustained responses or stable disease. Cancer 2008. © 2008 American Cancer Society.
Novel 2‐step synthetic indole compound 1,1,3‐tri(3‐indolyl)cyclohexane inhibits cancer cell growth in lung cancer cells and xenograft models
Authors: Lee Ching‐Hsiao , Yao Ching‐Fa , Huang Sin‐Ming , Ko Shengkai , Tan Yi‐Hung , Lee‐Chen Guey‐Jen , Wang Yi‐Ching 
Published: July 2008

AbstractBACKGROUND.The clinical responses to chemotherapy in lung cancer patients are unsatisfactory. Thus, the development of more effective anticancer drugs for lung cancer is urgently needed.METHODS.A 2‐step novel synthetic compound, referred to as 1,1,3‐tri(3‐indolyl)cyclohexane (3‐indole), was generated in high purity and yield. 3‐Indole was tested for its biologic activity in A549, H1299, H1435, CL1‐1, and H1437 lung cancer cells. Animal studies were also performed.RESULTS.The data indicate that 3‐indole induced apoptosis in various lung cancer cells. Increased cytochrome‐c release from mitochondria to cytosol, decreased expression of antiapoptotic Bcl‐2, and increased expression of proapoptotic Bax were observed. In addition, 3‐indole stimulated caspases‐3, ‐9, and to a lesser extent caspase‐8 activities in cancer cells, suggesting that the intrinsic mitochondria pathway was the potential mechanism involved in 3‐indole‐induced apoptosis. 3‐Indole‐induced a concentration‐dependent mitochondrial membrane potential dissipation and an increase in reactive oxygen species (ROS) production. Activation of c‐Jun N‐terminal kinase (JNK) and triggering of DNA damage were also apparent. Note that 3‐indole‐induced JNK activation and DNA damage can be partially suppressed by an ROS inhibitor. Apoptosis induced by 3‐indole could be abrogated by ROS or JNK inhibitors, suggesting the importance of ROS and JNK stress‐related pathways in 3‐indole‐induced apoptosis. Moreover, 3‐indole showed in vivo antitumor activities against human xenografts in murine models.CONCLUSIONS.On the basis of its potent anticancer activity in cell and animal models, the data suggest that this 2‐step synthetic 3‐indole compound of high purity and yield is a potential candidate to be tested as a lead pharmaceutical compound for cancer treatment. Cancer 2008. © 2008 American Cancer Society.
Aggressiveness of care in a prospective cohort of patients with advanced NSCLC
Authors: Temel Jennifer S. , McCannon Jessica , Greer Joseph A. , Jackson Vicki A. , Ostler Patricia , Pirl William F. , Lynch Thomas J. , Billings J. Andrew 
Published: July 2008

AbstractBACKGROUND.Optimal end of life care of patients with terminal cancer is poorly understood. In this study, the aggressiveness of care is described in a cohort of patients with newly diagnosed advanced nonsmall‐cell lung cancer (NSCLC).METHODS.Patients within 8 weeks of diagnosis of stage IIIb (with effusions) or IV NSCLC were enrolled in a study to examine the feasibility of involving palliative care services early in the provision of cancer care. Participants received standard oncology treatment and integrated palliative care. All patients were followed prospectively to assess anticancer therapy usage, hospital admissions, hospice utilization, and location of death.RESULTS.At the time of analysis, 40/46 (87%) of enrolled patients had died, with a median length of follow‐up of 29.3 months. Aggressive care measures in the final month of life included rates of anticancer therapy (40%), emergency department visits (48%), and hospital admissions (50%). Sixty‐five percent of patients received hospice care before death, with a median length of stay of 16 days. Patients with heightened baseline anxiety and mood symptoms were more likely to receive anticancer therapy at the end of life compared with those without such symptoms.CONCLUSIONS.This study demonstrates the frequent use of aggressive measures at the end of life among patients with advanced NSCLC in a tertiary care center, as shown by the number of patients receiving anticancer therapy within 30 days of death and brief utilization of hospice services. Further research is needed to identify predictors of aggressive care and to develop interventions enhancing decision‐making at the end of life. Cancer 2008. © 2008 American Cancer Society.
Racial/ethnic differences in adequacy of information and support for women with breast cancer
Authors: Janz Nancy K. , Mujahid Mahasin S. , Hawley Sarah T. , Griggs Jennifer J. , Hamilton Ann S. , Katz Steven J. 
Published: July 2008

AbstractBACKGROUND.Providing breast cancer patients with needed information and support is an essential component of quality care. This study investigated racial/ethnic variations in the information received and in the availability of peer support.METHODS.In total, 1766 women who were diagnosed with nonmetastatic breast cancer and reported to the Los Angeles County Surveillance, Epidemiology, and End Results registry from June 2005 to May 2006 were mailed a survey after initial treatment. Among accrued cases, 96.2% met eligibility criteria (n = 1698), and 72% completed the survey. Race/ethnicity categories were white, African American, and Latinas (2 categories indicating low or high acculturation, which was determined by using the Short Acculturation Scale for Hispanics). Outcomes included receipt and need for treatment‐related and survivorship‐related information, difficulty understanding information, and support from women with breast cancer.RESULTS.More women reported receiving treatment‐related information than survivorship‐related information. After adjusting for sociodemographic, clinical, and treatment factors, a higher percentage of low acculturated Latina women desired more information on treatment‐related and survivorship‐related issues (P < .001). Significantly more Latina low acculturated women than white women reported difficulty understanding written materials, with 74.5% requiring help from others. A higher percentage of all minority groups compared with whites reported no contact with other women with breast cancer (P < .05) and reported less contact through family/friends (P < .05). Women rated the benefit of talking to other women high, particularly with emotional issues.CONCLUSIONS.Continued efforts to provide culturally appropriate information and support needs to women with breast cancer are necessary to achieve quality care. Latinas with low acculturation reported more unmet information and care support needs than women in other racial/ethnic groups. Cancer 2008. © 2008 American Cancer Society.
Growth rates of metastatic brain tumors in nonsmall cell lung cancer
Authors: Yoo Heon , Nam Byung‐Ho , Yang Hee‐Seok , Shin Sang Hoon , Lee Jin Soo , Lee Seung Hoon 
Published: July 2008

AbstractBACKGROUND.The purpose of the study was to evaluate the growth kinetics of metastatic brain tumors during chemotherapy and to analyze growth rates and volumetric doubling time of metastatic brain tumors in patients with nonsmall cell lung cancer (NSCLC) with tumor regrowth.METHODS.NSCLC patients with minimally symptomatic brain metastases who were not treated previously were enrolled. Serial magnetic resonance images (MRI) of 30 metastatic brain tumors in 19 patients were reviewed. Tumor growth rates and volumetric tumor doubling time of tumor regrowth were estimated. All patients were treated with front‐line chemotherapy until disease progression.RESULTS.The median tumor growth rate was 12.10 mm3/day (interquartile range [IQR], 3.09‐36.75). The volume percentage increase/day was 1.67 (IQR, 0.69‐4.59). The median volumetric tumor doubling time was 58.48 days (IQR, 32.33‐98.48).CONCLUSIONS.These findings may help optimize patient management during follow‐up. Study results indicated that brain MRI should be obtained at a minimum of 2‐month intervals to screen for metastatic brain tumors. Cancer 2008. © 2008 American Cancer Society.
Hypoxia‐regulated protein expression, patient characteristics, and preoperative imaging as predictors of survival in adults with glioblastoma multiforme
Authors: Flynn Jeannette R. , Wang Libo , Gillespie David L. , Stoddard Gregory J. , Reid Jason K. , Owens Jason , Ellsworth Grant B. , Salzman Karen L. , Kinney Anita Y. , Jensen Randy L. 
Published: July 2008

AbstractBACKGROUND.Regions of hypoxia within glioblastoma multiforme (GBM) are common and may influence a tumor's aggressiveness, response to treatment, and the patient's overall survival. In this study, the authors examined 4 markers of hypoxia (hypoxia‐inducible factor 1 [HIF‐1α], glucose transporter 1 [GLUT‐1], vascular endothelial growth factor [VEGF], and carbonic anhydrase 9 [CA IX]), cellular proliferation and microvascular density (MVD) indices, extent of surgical resection, and preoperative imaging characteristics and compared them with the overall survival rates of adults with GBM.METHODS.In this retrospective cohort study, patients who had lower grade astrocytomas were compared with patients who had GBM to verify that the methods used could establish differences between tumor grades. By using preoperative imaging, the amount of necrosis was established versus the overall tumor area. The authors also compared preoperative images with postoperative images to define the amount of tumor resected; and they compared molecular markers, proliferation, MVD, and imaging studies with survival among patients who had GBM.RESULTS.The hypoxia‐regulated molecules (HRMs) and indices for MVD and cellular proliferation were associated significantly with tumor grade. Survival was improved when ≥95% of the tumor was resected. Although the total tumor area was associated with overall survival, no differences were observed when the amount of necrosis or a tumor necrosis index (area of necrosis/area of tumor) was compared with survival. The findings indicated that GLUT‐1 and VEGF were correlated with survival after controlling for age.CONCLUSIONS.Tumor grade was differentiated with HRMs, MVD, and proliferation, but only GLUT‐1 predicted survival in this group of patients with GBM. The results suggested that GLUT‐1 may be an important independent prognostic indicator. Cancer 2008. © 2008 American Cancer Society.
Never‐smoking nonsmall cell lung cancer as a separate entity
Authors: Yano Tokujiro , Miura Naoko , Takenaka Tomoyoshi , Haro Akira , Okazaki Hiroshi , Ohba Taro , Kouso Hidenori , Kometani Takuro , Shoji Fumihiro , Maehara Yoshihiko 
Published: July 2008

AbstractBACKGROUND.To propose ‘never‐smoking nonsmall cell lung cancer (NSCLC)’ as a separate entity, the clinicopathologic differences of operable NSCLC between never‐smoking patients and patients with a history of smoking were investigated.METHODS.The medical records of 1405 patients with primary NSCLC who underwent a complete resection at the study institution from 1974 through 2004 were reviewed for clinicopathologic variables and postoperative survival.RESULTS.The proportion of never‐smoking patients with NSCLC has been significantly increasing over 30 years, from 15.9% in the 1970s to 32.8% in the 2000s. A significantly greater proportion of female patients or adenocarcinoma patients was found in the ‘never‐smoking NSCLC’ group in comparison to the ‘smoking NSCLC’ group (85.8% vs 11.2% and 87.8% vs 49.1%, respectively). The proportion of pathologic stage IA disease for the ‘never‐smoking NSCLC’ group was significantly higher than that for the ‘smoking NSCLC’ group (40.1% vs 25.4%; P < .0001). With regard to both overall and cancer‐specific survival, the ‘never‐smoking NSCLC’ patient group was significantly superior to the ‘smoking NSCLC’ group. In addition to smoking status, the factors found to be significantly associated with the postoperative survival rate were sex, histologic type, T classification, and N classification by univariate analyses. A multivariate analysis revealed never‐smoking status to be an independent prognostic factor in addition to pathologic T and N classification.CONCLUSIONS.The differences in the clinicopathologic factors and survivals between the ‘never‐smoking NSCLC’ patient group and the ‘smoking NSCLC’ group suggest that NSCLC in never‐smokers should be considered a separate disease entity. Cancer 2008. © 2008 American Cancer Society.
Heparanase is overexpressed in lung cancer and correlates inversely with patient survival
Authors: Cohen Esti , Doweck Ilana , Naroditsky Inna , Ben‐Izhak Ofer , Kremer Ran , Best Lael A. , Vlodavsky Israel , Ilan Neta 
Published: July 2008

AbstractBACKGROUND.Heparanase is an endo‐β‐D‐glucuronidase that is capable of cleaving heparan sulfate (HS) side chains at a limited number of sites, yielding HS fragments of still appreciable size (approximately 5‐7 kDa). Heparanase activity has been detected frequently in several cell types and tissues. Heparanase activity correlates with the metastatic potential of tumor‐derived cells, a correlation that has been attributed to enhanced cell dissemination as a consequence of HS cleavage and remodeling of the extracellular matrix barrier.METHODS.In this study, the authors examined heparanase expression in 114 patients with lung cancer by means of immunohistochemistry and correlated clinical‐pathologic data with heparanase immunostaining and cellular localization.RESULTS.Heparanase was overexpressed in 75% of the study patients. Heparanase expression was correlated with lung cancer lymph node status and metastasis classification (P = .04 and P = .01, respectively) and was correlated inversely with patient survival (P = .007). It is noteworthy that this adverse effect depended largely on the cellular localization of heparanase. Thus, whereas cytoplasmic staining of heparanase is associated with a poor prognosis, nuclear heparanase predicts a favorable outcome for patients with lung cancer.CONCLUSIONS.The current findings suggest that heparanase expression and cellular localization are decisive for lung cancer patients' prognosis, most likely because of heparanase‐mediated tumor cell dissemination by blood and lymph vessels. Cancer 2008. © 2008 American Cancer Society.
Randomized trial of a decision aid for individuals considering genetic testing for hereditary nonpolyposis colorectal cancer risk
Authors: Wakefield Claire E. , Meiser Bettina , Homewood Judi , Ward Robyn , O'Donnell Sheridan , Kirk Judy ,   and the Australian GENetic testing Decision Aid Collaborative Group
Published: July 2008

AbstractBACKGROUND.Despite the potential benefits of genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) risk, individuals can find the genetic testing decision‐making process complicated and challenging. The goal of the current study was to measure the effectiveness of a tailored decision aid designed specifically to assist individuals to make informed decisions regarding genetic testing for HNPCC risk.METHODS.In all, 153 individuals were randomized to receive the decision aid or a control pamphlet at the end of their first genetic counseling consultation. Of these, 109 (71.2%) completed the first questionnaire 1 week after consultation, whereas 95 (62.1%) completed the 6‐month follow‐up questionnaire.RESULTS.Although the decision aid had no significant effect on postdecisional regret or actual genetic testing decision, the trial results demonstrated that participants who received the decision aid had significantly lower levels of decisional conflict (ie, uncertainty) regarding genetic testing (chi‐square(1) = 8.97; P = .003) and were more likely to be classified as having made an informed choice concerning genetic testing (chi‐square(1) = 4.37; P = .037) than participants who received a control pamphlet. Also, men who received the decision aid had significantly higher knowledge levels regarding genetic testing compared with men who received the control pamphlet, whereas no such differences were found for women (chi‐square(2) = 6.76; P = .034).CONCLUSIONS.A decision aid for individuals considering genetic testing for HNPCC is an effective intervention to reduce uncertainty and assist individuals to make an informed choice regarding genetic testing for HNPCC after genetic counseling. Cancer 2008. © 2008 American Cancer Society.
Patterns of care for women with cervical cancer in the United States
Authors: Trimble Edward L. , Harlan Linda C. , Gius David , Stevens Jennifer , Schwartz Stephen M. 
Published: July 2008

AbstractBACKGROUND.Recommendations for pretreatment evaluation and treatment of cervical cancer have significantly evolved over the last decade because of the results of multiple randomized studies comparing the addition of platin‐based chemoradiation as well as the widespread dissemination and use of imaging modalities. This analysis was initiated to determine any systemic changes in management of cervical cancers.METHODS.Surveillance, Epidemiology, and End Results program data were used to sample newly diagnosed women in 1997, 2000, and 2001 with cancer of the cervix. A total of 3116 women with no previous diagnosis of cancer were selected. Data were reabstracted, additional information not routinely collected was obtained, therapy was verified with the treating physician, and multiple endpoints were analyzed.RESULTS.A marked rise was observed in the percentage receiving chemotherapy (34% to 85%) as well as concurrent chemoradiation (20% to 72%) from 1997 to 2001.CONCLUSIONS.The significant change in the management and treatment of cervical cancer appears to correspond temporally with the publication of 5 clinical trials, all of which showed a significant improvement in overall survival associated with chemoradiation. This change also corresponded with the NCI Clinical Announcement that was disseminated in 1999 to those oncologists most likely to treat women with cervical cancer. Cancer 2008. © 2008 American Cancer Society.
Differential cytotoxicity of novel somatostatin and dopamine chimeric compounds on bronchopulmonary and small intestinal neuroendocrine tumor cell lines
Authors: Kidd Mark , Drozdov Ignat , Joseph Richard , Pfragner Roswitha , Culler Michael , Modlin Irv 
Published: July 2008

AbstractBACKGROUND.Survival rates for gastrointestinal (GI) and bronchopulmonary (BP) neuroendocrine tumors (NETs) have not significantly altered (overall 67%, 5‐year survival) in 30 years (1973‐2004), whereas the incidence has increased (∼ 1000%) in the same time frame. No effective or specific antineoplastic agent is available for treatment, although somatostatin analogs inhibit tumor secretion. Given the coexistence of somatostatin and dopamine regulatory receptors on NET cells, the antiproliferative efficacy as well as the signaling and transcriptional targets of their ligands were evaluated.METHODS.The cytotoxic effects of 12 somatostatin/dopamine compounds were evaluated in 3 NET cell lines, and real‐time polymerase chain reaction and enzyme‐linked immunoadsorbent assay studies were performed to delineate antiproliferative signaling pathways.RESULTS.The atypical BP‐NET, NCI‐H720, was most sensitive to the sst5 analog BIM23206 (half‐maximal concentration, 2.4 pM) and demonstrated similar sensitivity to lanreotide and the sst2 analog BIM23120. The typical BP‐NET, NCI‐H727, was most sensitive to BIM23120 (0.7 nM) and to the pan‐somatostatin receptor analog (BIM23A779). The GI‐NET, KRJ‐I, was most sensitive to sst2,5 analogs lanreotide (1 nM) and BIM23244 (7.4 nM). Lanreotide activated extracellular signal regulated kinase‐1/2 phosphorylation and p21WAF1/CIP1 transcription, but inhibited Ki‐67 transcription. NCI‐H720 was most sensitive to the sst2,5‐ and D2‐selective compound BIM23A761 (4.2 nM), as was NCI‐H727 (5.5 nM). KRJ‐I did not respond to any chimeric analog. BIM23A761 activated c‐Jun N‐terminal kinase signaling and caused inhibition of Ki‐67 transcription. P21WAF1/CIP1 transcription was activated only in NCI‐H727 cells.CONCLUSIONS.The different responses of each individual cell line suggested that NETs from different locations arising from different neuroendocrine cells may require cell‐specific antiproliferative agents based on the unique receptor profile of individual lesions. Cancer 2008. © 2008 American Cancer Society.