bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Subsets Benefiting from Adjuvant Therapy Following Surgical Resection of Non–Small Cell Lung Cancer
Authors: Johnson Bruce E. , Rabin Michael S. 
Published: September 2005

Abstract
Adjuvant chemotherapy is the standard of therapy for some patients with stages I, II, and III breast and colon cancer. The therapeutic efficacy of adjuvant chemotherapy following surgical resection of early stage non–small cell lung cancer (NSCLC) has been less clear. A meta-analysis was reported in 1995 of patients who underwent surgical resection for early stage NSCLC and were then randomized to either observation or chemotherapy. This meta-analysis showed a 13% reduction in the hazard ratio of death, leading to a 5% absolute improvement in survival 5 years after the start of adjuvant cisplatin-based chemotherapy treatment compared with observation only. Multiple prospective randomized trials for patients with NSCLC were planned and undertaken to attempt to validate the observations of the meta-analysis. Six trials with ≥150 patients with early stage NSCLC (stages I-IIIA) on each arm have been reported in the last 2 years. Four of the six trials show a survival advantage for the patients with early stage NSCLC treated with adjuvant chemotherapy compared with those who underwent observation. The survival benefit in these four studies varies from a 4% to a 16% survival advantage at 4 to 5 years after the start of chemotherapy. The hazard ratio of death for the patients treated with chemotherapy ranged from 0.61 to 0.86 compared with patients on observation. Thus, the information available at the current time supports the administration of chemotherapy for patients with stages IB and II NSCLC. Further research will be needed to define the role of adjuvant chemotherapy and its use in conjunction with chest radiotherapy for the treatment of patients with resected stages IA and IIIA NSCLC.
Surgical Management of T3 and T4 Lung Cancer
Authors: DiPerna Costanzo A. , Wood Douglas E. 
Published: September 2005

Abstract
Locally advanced lung cancer (T3 or T4) has a significantly worse prognosis than lower stage disease. However, this diagnosis is usually made radiologically, and experienced thoracic surgeons are familiar with the low radiologic to pathologic correlation in tumors that abut the great vessels, mediastinum, or chest wall. Commonly these tumors do not directly invade adjacent structures and are, in fact, T1 or T2 tumors that are resectable through standard techniques. Where there is no clearly evident invasion of unresectable structures, the patient should be given the benefit of the doubt and considered at a lower (resectable) stage until proven otherwise. The curability of T3 tumors varies according to the involved site. A T3N0 tumor involving the chest wall provides the most favorable prognosis among the resected T3 lesions, with a 5-year survival of &gt;50% in lymph node–negative patients if resection is complete. Palliative incomplete resections of T4 disease, in which tumor has invaded mediastinal structures, have not shown any survival benefit and are associated with very high morbidity and mortality. However, patients with limited invasion of the carina, left atrium, superior vena cava, or pulmonary artery may be able to be completely resected despite their T4 classification. Surgical resection remains an important part of the therapy for patients with locally advanced lung cancer. Modern techniques of chest wall resection and reconstruction and bronchoplastic procedures allow complete resection of locally advanced tumors with favorable 5-year survival rates and low morbidity and mortality.
The Role of Surgery in N2 Non–Small Cell Lung Cancer
Authors: DeCamp Malcolm M. , Ashiku Simon , Thurer Robert 
Published: September 2005

Abstract
Historical series document the poor survival (7-16% at 5 years) for patients with N2-positive, stage IIIA non–small cell lung cancer (NSCLC) treated with primary surgery. In 1994, two small randomized trials showed the superiority of induction chemotherapy followed by surgery over surgery alone for stage IIIA NSCLC. These findings, as well as subsequent studies showing the superiority of chemoradiotherapy over chemotherapy alone in nonoperable stage III disease, prompted investigations of preoperative chemoradiotherapy for N2-positve patients. As induction therapy improved, the use of resection in stage IIIA NSCLC was called into question. An Intergroup trial addressing this issue randomized 392 patients to induction chemoradiotherapy followed by surgery versus definitive chemoradiotherapy. Surgery following induction chemoradiotherapy was associated with a significant improvement in progression-free survival and almost a 50% reduction in local failure. As distant relapse is common, survival is likely to be enhanced only in those patients who respond to the systemic arm of treatment. Identification of genetic or biochemical markers of response, minimally invasive techniques to pathologically restage, or improved statistical or chemosensitivity analyses are needed to enhance our ability to select patients who will benefit from resection.
Novel Antiangiogenic Therapies for Renal Cell Cancer
Authors: Gordon Michael S. 
Published: September 2005

Abstract
Renal cell cancer remains a disease for which highly effective therapy for the majority of patients with metastatic disease is lacking. The biology of clear cell carcinomas and their association with mutations of the von Hippel-Lindau gene and its resultant increased expression of vascular endothelial growth factor (VEGF) make angiogenesis a potentially pathophysiologic mechanism for tumor development. As a result, the use of antiangiogenic therapy is an intriguing concept for the treatment of renal cell cancer. Various agents, aside from the inhibitors of VEGF, have been studied, including thalidomide, low-dose interferon, and novel antiangiogenic agents such as the thrombospondin-1 mimetics. Use of these agents has been associated with some degree of objective response or prolonged stabilization of disease, and their true value needs to be assessed in ongoing prospective studies. Combinations of antiangiogenic agents either with other similarly acting drugs or as a component of a “cocktail” with other noncytotoxic therapies should be explored in this patient population.
Nonmyeloablative Transplantation
Authors: Takahashi Yoshiyuki , Childs Richard W. 
Published: September 2005

Abstract
High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation has been explored as a method to enhance the efficacy of chemotherapy for advanced solid tumors. The failure of autologous hematopoietic stem cell transplantation to prolong survival in patients with metastatic solid tumors has sparked interest recently in studies exploring the potential of allogeneic hematopoietic stem cell transplantation for such patients. Allogeneic hematopoietic stem cell transplantation is widely accepted as a potent form of immunotherapy capable of curing patients with chemotherapy-refractory hematologic malignancies. However, it was not until the end of the 20th century that investigators initiated trials to test the potential of allogeneic hematopoietic stem cell transplantation as immunotherapy in malignancies of epithelial origin. Early pilot trials have established proof-of-principle that graft-versus-tumor effects can induce complete or partial remission in some treatment-refractory metastatic solid tumors. In this review, we discuss the rationale for pilot trials investigating the potential of nonmyeloablative allogeneic hematopoietic stem cell transplantation in advanced cytokine-refractory renal cancer, highlighting the preliminary success, limitations, and future clinical directions of this approach.
Effect of Renal Cell Carcinomas on the Development of Type 1 T-Cell Responses
Authors: Rayman Patricia , Wesa Amy K. , Richmond Amy L. , Das Tanya , Biswas Kaushik , Raval Gira , Storkus Walter J. , Tannenbaum Charles , Novick Andrew , Bukowski Ronald , Finke James 
Published: September 2005

AbstractPurpose: We reported that in renal cell carcinoma patients with active disease, T-cell reactions to the tumor-associated antigens MAGE-6 and EphA2 are highly skewed toward TH2-type cytokine responses [interleukin (IL) 5]. Herein, we determined whether tumor-derived products, including gangliosides isolated from renal cell carcinoma patients, participate in the down-regulation of type 1 T-cell responses.Experimental Design: T cells from healthy volunteers or renal cell carcinoma patients were cultured in the presence and absence of supernatants derived from renal cell carcinoma explants or with gangliosides isolated from those tumor supernatants. T cells were stimulated or not with either autologous dendritic cells pulsed with superantigen (Staphylococcus enterotoxin B) or with phorbol 12-myristate 13-acetate and ionomycin and then were assessed for type 1 or type 2 responses (cytokine production and gene expression) and apoptosis.Results: Tumor supernatants efficiently inhibited the TH1-type responses [interferon (IFN) γ] of T cells stimulated with either S. enterotoxin B or phorbol 12-myristate 13-acetate and ionomycin but had no inhibitory effect on activated T-cell production of type 2 cytokines (IL-4, IL-5, and IL-10). Likewise, IFN-γ mRNA and protein production were inhibited when T cells were cocultured with either renal cell carcinoma supernatant-derived gangliosides or a commercial source of purified GD1a. It was also determined that gangliosides impair type 1 responses by inducing apoptosis of activated T cells.Conclusions: We propose that renal cell carcinoma-derived tumor products such as gangliosides can induce a type 2 bias in antitumor immunity by initiating apoptosis in the IFN-γ-producing type 1 effector cells. This represents a relevant mechanism by which renal cell carcinoma can inhibit protective antitumor immunity.
Detection of Micrometastatic Disease and Monitoring of Perioperative Tumor Cell Dissemination in Primary Operable Breast Cancer Patients Using Real-Time Quantitative Reverse Transcription-PCR
Authors: Ismail Mohamed Saad , Wynendaele Wim , Aerts Joeri L. E. , Paridaens Robert , Gaafar Rabab , Shakankiry Nayera , Khaled Hussein M. , Christiaens Marie-Rose , Wildiers Hans , Omar Sherif , Vandekerckhove Philippe , van Oosterom Allan T. 
Published: September 2005

Abstract
Purpose: We previously found a statistically significant number of cytokeratin 19 (CK19)+ cells in peripheral blood (PB) of stage IV breast cancer (BC) patients compared with those of healthy volunteers, using a quantitative real-time reverse transcription-PCR. We aimed to apply the technique on bone marrow (BM) of primary operable BC patients. Pre- and postoperative PB samples of these patients were further analyzed to investigate possible shedding of CK19+ cells during the operation.
Experimental Design: In 54 primary operable BC patients, we analyzed 50 BM samples taken preoperatively and 297 PB samples. PB samples were collected before surgery; immediately after surgery; on the first, second, and fifth day postoperatively; and one month postoperatively.
Results: In BM of controls and BC patients, we detected a median of 28 and 568 CK19+ cells/5 × 106 leukocytes, respectively (P &lt; 0.001). In preoperative blood (B-1) samples, we measured a median of 109 CK19+ cells. Using the upper limit of 95% confidence interval of controls as cutoff, 74% and 52% of BM and (B-1), respectively were considered CK19+. There was no significant correlation between CK19+ cells in BM and (B-1) and classical prognostic factors. We found no significant difference between blood samples at different time points with respect to the average CK19+ cells.
Conclusions: In primary BC patients, we detected high numbers of CK19+ cells in BM and PB (B-1) samples compared with controls. However, no significant correlation between the presence of CK19+ cells in BM and PB and classical prognostic factors was found. We detected no statistically significant influence of surgical manipulation on CK19+ cells.
Detection of Residual Subclinical Ovarian Carcinoma after Completion of Adjuvant Chemotherapy
Authors: Nouriani Mory , Bahador Afshin , Berek Jonathan S. , Cheng Joan P. , Chi Dennis S. , Cliby William A. , Del Priore Giuseppe , Dodson Mark K. , Duggan Bridgette D. , Gershenson David M. , Lentz Scott E. , Penson Richard T. , Robinson William R. , Rodriguez Mildred , Roman Lynda D. , Yu Mimi C. , Zempolich Karen , Dubeau Louis 
Published: September 2005

Abstract
Purpose: We sought to test the hypothesis that the presence of telomerase activity in peritoneal washings of patients treated for ovarian carcinoma is a sensitive and specific indicator of the presence of residual disease. We hypothesized that this test, if added to second-look procedure protocols, could help determine whether residual disease is present or not in patients who have completed their adjuvant chemotherapy for ovarian carcinoma.
Experimental Design: Peritoneal washings were obtained from 100 consecutive patients undergoing a second-look procedure after treatment for ovarian carcinoma (cases) and from 100 patients undergoing surgery for benign gynecological conditions (controls). The washings were assayed for telomerase activity using the telomerase repeat amplification protocol. The results were compared to the histological and cytological findings.
Results: Among our 100 cases, 82 (82%) had either positive second-look procedures or expressed telomerase in their peritoneal washings. Fifty-three (53%) had positive second-look procedures, whereas 66 (66%) tested positive for telomerase. Twenty-nine of the 47 patients (62%) with negative second-look procedures tested positive for telomerase. Of the 53 patients with positive second-look procedures, 37 (70%) tested positive for telomerase. None of the 100 controls (0%) expressed telomerase in their peritoneal washings.
Conclusions: Telomerase activity in peritoneal washings of patients treated for ovarian carcinoma and undergoing a second-look procedure may provide a means of increasing the sensitivity of such procedures for the detection of residual disease while maintaining a high level of specificity.
Predictive Markers for Late Cervical Metastasis in Stage I and II Invasive Squamous Cell Carcinoma of the Oral Tongue
Authors: Lim Sang-Chul , Zhang Shichuan , Ishii Genichiro , Endoh Yasushi , Kodama Keiji , Miyamoto Shinichi , Hayashi Ryuichi , Ebihara Satoshi , Cho Jae-Shik , Ochiai Atsushi 
Published: September 2005

Abstract
Purpose: Patients with oral tongue carcinoma treated by intraoral excision only should be followed up carefully for cervical lymph node metastasis and salvaged immediately if found, because some patients have a more aggressive clinical course. The purpose of this study was to find useful markers for predicting late cervical metastasis in patients with stage I and II invasive squamous cell carcinoma of the oral tongue.
Experimental Design: We investigated clinicopathologic factors and immunohistochemical biomarkers predicting late cervical metastasis in surgical specimens from 56 patients with T1–2N0M0 invasive squamous cell carcinoma of the oral tongue who did not undergo elective neck dissection. Histopathologic factors including tumor thickness, mode of invasion, Broders grade, total score of three different malignancy grading systems, eight other clinicopathologic parameters, and immunohistochemical expression of p53, cyclin D1, Ki-67, epidermal growth factor receptor, microvessel density, cyclooxygenase-2, MUC1, laminin-5 γ2, E-cadherin, and β-catenin were examined. All of the clinicopathologic factors and immunohistochemical expression of biomarkers were compared in terms of survival.
Results: In the univariate analysis, tumor thickness (P = 0.009), Broders grade (P = 0.017), nest shape (P = 0.005), mode of invasion (P &lt; 0.001), Anneroth score (P = 0.029), Bryne score (P &lt; 0.001), and E-cadherin expression (P = 0.003) were correlated with late cervical metastasis. Multivariate analysis on late cervical metastasis revealed that tumor thickness &gt;4 mm, mode of invasion grade 3 or 4, and E-cadherin expression were independent factors. Late cervical metastasis was the only prognostic factor for overall survival (P = 0.002).
Conclusions: Our results indicate that patients with stage I and II invasive squamous cell carcinoma of the oral tongue with tumor thickness &gt;4 mm, mode of invasion grade 3 or 4, and low expression of E-cadherin should be considered a high-risk group for late cervical metastasis when a wait-and-see policy for the neck is adopted.
Osteopontin But Not Osteonectin Messenger RNA Expression Is a Prognostic Marker in Curatively Resected Non-Small Cell Lung Cancer
Authors: Schneider Sylke , Yochim JiMin , Brabender Jan , Uchida Kazumi , Danenberg Kathleen D. , Metzger Ralf , Schneider Paul M. , Salonga Dennis , Hölscher Arnulf H. , Danenberg Peter V. 
Published: September 2005

AbstractPurpose: The purpose of this study was to better define the role of osteopontin (OPN) and osteonectin [also known as secreted protein acidic and rich in cysteine (SPARC)] in lung tumorigenesis by comparing the expressions of these genes in lung tumor tissue and matched normal tissue and by determining the prognostic significance of the gene expressions.Experimental Design: Quantitative real-time reverse transcription-PCR was used to analyze OPN and SPARC mRNA expression in normal lung tissue and matching tumor samples from 82 patients with non-small cell lung cancer. Gene expression data for each patient were matched to survival data.Results: The overall median mRNA expression level of OPN was about 20-fold higher in tumor tissues than in matching normal lung tissues (P &lt; 0.001), whereas SPARC gene expression was not significantly different in both tissue types. Forty of 82 patients had high (≥4.1) intratumoral OPN expression, and 15 of 82 patients had high (≥15.5) SPARC expression. High OPN expression in the tumor tissue was associated with inferior survival (P = 0.014), whereas high SPARC expression showed a trend toward longer survival (P = 0.095). The impact of high OPN and low SPARC expression on patient survival was additive (P = 0.001).Conclusions: The large increase in OPN expression in tumors compared with normal tissue and its association with survival suggest a role for OPN in lung tumorigenesis.
Nuclear Factor-κB Is Constitutively Activated in Prostate Cancer
In vitro
and Is Overexpressed in Prostatic Intraepithelial Neoplasia and Adenocarcinoma of the Prostate
Authors: Sweeney Christopher , Li Lang , Shanmugam Rajasubramaniam , Bhat-Nakshatri Poornima , Jayaprakasan Vetrichelvan , Baldridge Lee Ann , Gardner Thomas , Smith Martin , Nakshatri Harikrishna , Cheng Liang 
Published: September 2005

Abstract
Purpose: The transcription factor nuclear factor-κB (NF-κB) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis.
Experimental Design: Electromobility gel shift assays were used to evaluate NF-κB DNA binding in vitro. The functional relevance of NF-κB DNA binding was assessed by both cDNA array analyses and proliferation assays of prostate cancer cells with and without exposure to an NF-κB inhibitor, parthenolide. Immunohistochemistry staining for the p65 NF-κB subunit was used to determine the frequency and location of NF-κB in 97 prostatectomy specimens. The amount of staining was quantified on a 0–3+ scale.
Results: An electromobility gel shift assay confirmed the presence of NFκB DNA binding in all four prostate cancer cell lines tested. The binding was inhibited by parthenolide, and this agent also decreased multiple gene transcripts under the control of NF-κB and inhibited proliferation of prostate cancer cells. The staining results revealed overexpression of p65 in the prostatic intraepithelial neoplasia and cancer compared with the benign epithelium. Specifically, there was a predominance of 1+ and 2+ with no 3+ staining in benign epithelium, whereas there was only 2+ and 3+ staining (30 and 70%, respectively) in the cancerous areas. These differences were statistically different. There was no correlation with tumor grade or stage.
Conclusions: NF-κB is constitutively activated in prostate cancer and functionally relevant in vitro. Immunohistochemistry of human prostatectomy specimens demonstrated overexpression of the active subunit of NF-κB, p65, and that this occurs at an early stage in the genesis of prostate cancer. This work supports the rationale for targeting NF-κB for the prevention and/or treatment of prostate cancer.
Gene Expression Profiles Predict Survival and Progression of Pleural Mesothelioma
Authors: Pass Harvey I. , Liu Zhandong , Wali Anil , Bueno Raphael , Land Susan , Lott Daniel , Siddiq Fauzia , Lonardo Fulvio , Carbone Michele , Draghici Sorin 
Published: September 2005

Abstract
Purpose: Clinical outcomes for malignant pleural mesothelioma (MPM) patients having surgery are imprecisely predicted by histopathology and intraoperative staging. We hypothesized that gene expression profiles could predict time to progression and survival in surgically cytoreduced pleural mesothelioma of all stages.
Experimental Design: Gene expression analyses from 21 MPM patients having cytoreductions and identical postoperative adjuvant therapy were performed using the U95 Affymetrix gene chip. Using both dChip and SAM, neural networks constructed a common 27 gene classifier, which was associated with either the high-risk and low-risk group of patients. Data were validated using real-time PCR and immunohistochemical staining. The 27 gene classifier was also used for validation in a separate set of 17 MPM patients from another institution.
Results: The groups predicted by the gene classifier recapitulated the actual time to progression and survival of the test set with 95.2% accuracy using 10-fold cross-validation. Clinical outcomes were independent of histology, and heterogeneity of progression and survival in early stage patients was defined by the classifier. The gene classifier had a 76% accuracy in the separate validation set of MPMs.
Conclusions: These data suggest that pretherapy gene expression analysis of mesothelioma biopsies may predict which patients may benefit from a surgical approach.