tbuckley/cabot-search huggingface dataset:
Expression of PD-L1 in primary urothelial carcinoma (UC).
Authors: Jingsong Zhang, Shohreh I Dickinson, Noel D Clark, Amber Lea Flaherty
Journal: Journal of Clinical Oncology (2013)

4541 Background: Engagement of programmed cell death-1 (PD-1), expressed on CD8+ T cells, with it ligand PD-L1(B7H1), expressed on tumor cells, results in T cell suppression and tumor protection. Antibodies against PD-1 or PD-L1 have reported impressive anti-tumor activities in phase I/II trials and are being tested in the phase 3 setting. Exploratory analysis indicated that expression of PD-L1 could be a predictive marker for response. Of note, urothelial carcinoma (UC) was not included in the early phase anti-PD1 or anti-PD-L1 studies. To explore anti-PD-L1 as a new treatment for this lethal disease, we assessed PD-L1 expression in UC. Methods: The relative mRNA abundance of PD-L1 mRNA in UC was studied in the Oncomine Bittner Multi-cancer dataset, which included a total of 1911 tumor samples. PD-L1 immunohistochemistry (IHC) was performed with rabbit monoclonal antibody against human PD-L1 on tissue microarrays with 83 formalin fixed paraffin embedded T1, T2 and T3 UC. IHC slides were reviewed by a genitourinary pathologist. A positive staining is defined when ≥ 5% of cancer cells had positive PD-L1 membrane and/or cytoplasmic staining. The IHC slides were scanned with the Aperio ScanScope XT and the immunopositivity of PD-L1 was quantitatively scored using commercial algorithms from the Aperio Toolbox and TissueStudio. The 1+, 2+, and 3+ score of each core was based on the dominant IHC staining intensity. Results: In the Bittner multi-cancer dataset, the log2 median mRNA intensities of PD-L1 in prostate cancer, clear cell renal cell carcinoma, colon cancer, UC of the bladder, ureter and squamous cell carcinoma of the bladder were 0.245, 0.528, 0.61, 0.81, 0.802, and 1.202 respectively. The overall PD-L1 IHC staining positivity was 45% in 83 primary UC samples. All six 3+ PD-L1 staining cores were grade 3 urothelial carcinomas and each core had more than 60% of cancer cells with 3+ PD-L1 membrane staining. Grade 3 cores also had the highest percentage of 2+ and 3+ PD-L1 positivity. No association was observed between T staging and PD-L1 staining intensity. Conclusions: PD-L1 is expressed in primary UC. We have obtained additional UC samples to correlate its expression with survival and its expression pattern with the pattern of tumor infiltrating lymphocytes.
Treatment of advanced-stage colorectal adenocarcinoma with fluorouracil and high-dose leucovorin calcium: a pilot study.
Authors: J D Hines, M H Zakem, D J Adelstein, Y M Rustum
Journal: Journal of Clinical Oncology (1988)

Thirty-one evaluable patients with measurable advanced colorectal carcinoma were entered into a pilot study that used weekly fluorouracil (5-FU) at the dose of 600 mg/m2 by bolus infusion administered midway during a two-hour leucovorin calcium infusion of 500 mg/m2. This regimen was repeated weekly for six doses. Twenty-seven of these patients (87%) were considered to be refractory to prior 5-FU therapy and four (13%) were previously untreated. All 31 patients successfully completed at least one 6-week cycle of this regimen with acceptable toxicity. The combined complete (CR) and partial response (PR) rate was 45% with another 25% of patients remaining stable. The 95% confidence levels for the responding patients are 27.6% and 62.7%, respectively. The remaining 30% of the patients had all received prior 5-FU therapy and progressed. All of the responding patients and 80% of the patients with stable disease received two or more cycles of this regimen after a 3- to 4-week interval off therapy. The median time to disease progression was 16.1 months for responding patients and 6.7 months for those patients with stable disease. The median survival for the responders was 20.6 months and for those with stable disease 9.8 months. The median survival for the nonresponding patients was 3.9 months. Toxicity included diarrhea in 70% of patients, skin rash (erythema) in 10%, stomatitis in 15%, nausea and vomiting in 25%, and myelosuppression in 10%. This study confirms and extends previous observations that demonstrate the improved efficacy of 5-FU when used with high-dose leucovorin in advanced colorectal carcinoma.
Suppression and Recovery of Immunologic Function After Bone Marrow Transplantation<xref ref-type="fn" rid="FN1">1</xref><xref ref-type="fn" rid="FN2">2</xref>
Authors: R P Witherspoon
Journal: JNCI Journal of the National Cancer Institute (1986)

Infections are common causes of death in patients undergoing bone marrow transplantation for aplastic anemia or leukemia. A better understanding of the immunologic recovery following marrow grafting may lead to clinical trials of which the goals are to improve immunologic reactivity and to decrease infection.
Karnofsky Memorial Lecture. Hereditary cancer: theme and variations.
Authors: A G Knudson
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.10.3280 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9336366 Karnofsky Memorial Lecture. Hereditary cancer: theme and variations. A G KnudsonxA G KnudsonSearch for articles by this author Show More Fox Chase Cancer Center, Philadelphia, PA 19111, USA. https://doi.org/10.1200/JCO.1997.15.10.3280 First Page PDF © 1997 by American Society of Clinical Oncology
Effect of a clinical decision support system on early action on immunological treatment failure in patients with HIV in Kenya: a cluster randomised controlled trial
Authors: Tom Oluoch, Abraham Katana, Daniel Kwaro, Xenophon Santas, Patrick Langat, Samuel Mwalili, Kimeu Muthusi, Nicky Okeyo, James K Ojwang, Ronald Cornet, Ameen Abu-Hanna, Nicolette de Keizer
Journal: The Lancet HIV (2015)
Unclassified renal cell carcinoma (RCC): Analysis of clinical and pathologic features
Authors: H. Siddaiah, A. R. Golshayan, P. Elson, M. Zhou, J. A. Garcia, R. M. Bukowski, B. I. Rini
Journal: Journal of Clinical Oncology (2008)

16044 Background: Unclassified RCC includes a heterogeneous group of tumors not fitting into other histological subtypes, with a highly variable clinical course. Characterization of clinical and pathologic features may assist in management of these patients (pts). Methods: Pathologic data from pts with unclassified RCC were reviewed by a single pathologist. Clinical characteristics, objective response to treatment, progression-free survival (PFS) and overall survival (OS) were examined. Prognostic factors for PFS and OS were assessed by univariable and multivariable analyses. Results: 52 pts with unclassified RCC were identified. All had prior nephrectomy, 56% were female, and the median age was 60 years (range, 37–87). Histologically, 60% (34/52) had clear cell components, 52% papillary components, 42% both clear-cell and papillary components and 25% had sarcomatoid elements. The majority (65%) had localized disease at diagnosis with 82% of these pts remaining disease free at a median follow-up of 20 months (mos; range 2–85 mos). Eighteen percent of the localized group subsequently developed metastatic RCC (mRCC) at a median of 4.9 mos (range 1.9–13.7 mos) after nephrectomy. In the 18 pts with synchronous mRCC, disease sites included retroperitoneal lymph nodes (82%), lungs (41%), liver (36%) and bone (18%). Ten mRCC pts received systemic therapy (sunitinib 6, sorafenib 3, bevacizumab 1) with 1/10 PR, 6/10 stable disease, and 3/10 with progressive disease as their best response. Overall 73% (16/22) of pts with mRCC progressed and 59% have died. Median PFS and OS are estimated as 5.9 and 14.0 months respectively. Larger tumor size (4.1 vs. 7.3 cm, p=0.02) and sarcomatoid differentiation (44% vs. 15%, p=0.02) were more frequent in pts with synchronous mRCC than in localized disease. In mRCC pts, a multivariable analysis demonstrated sarcomatoid differentiation and number of metastatic sites as independent predictors of PFS. For OS, performance status and sarcomatoid differentiation were independent predictors. Conclusions: Pts with unclassified RCC appear to have a distinct clinical behavior compared to conventional clear-cell RCC with a higher rate of metastatic disease and poorer clinical outcomes. The presence of sarcomatoid elements may be a risk factor in these pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Antigenics, Bayer, Genentech™ BioOncology, Novartis, Onyx, Pfizer Oncology, Wyeth Bayer, Genentech™ BioOncology, Novartis, Onyx, Pfizer Oncology, Wyeth Bayer, Genentech™ BioOncology, Pfizer Oncology, Wyeth
Autologous cytokine-induced killer cell transfusion increases overall survival in advanced pancreatic cancer
Authors: Zibing Wang, Yuqing Liu, Rui’e Li, Yiman Shang, Yong Zhang, Lingdi Zhao, Wei Li, Yonghao Yang, Xiaojie Zhang, Tiejun Yang, Changfu Nie, Feng Han, Ying Liu, Suxia Luo, Quanli Gao, Yongping Song
Journal: Journal of Hematology & Oncology (2016)

Advanced pancreatic cancer (PC) has very poor prognosis with present treatments, thus necessitating continued efforts to find improved therapeutic approaches. Both preclinical and preliminary clinical data indicate that cytokine-induced killer (CIK) cells are an effective tool against various types of solid tumors. Here, we conducted a study to determine whether CIK cell-based therapy (CBT) can improve the outcomes of advanced PC. Eighty-two patients with advanced PC, whose predicted survival time was longer than 3 months, were analyzed retrospectively. Of all the patients, 57 individuals were receiving chemotherapy, while the remaining 25 individuals were treated with CBT. The overall survival analysis was based on 48 deaths in the 57 patients in the chemotherapy group (84.2 %) and 18 deaths in the 25 patients in the CBT group (72.0 %). In the CBT group, the median overall survival time was 13.5 months, as compared to 6.6 months in the chemotherapy group (hazard ratio for death, 0.39; 95 % confidence interval, 0.23 to 0.65; p < 0.001). The survival rate was 88.9 % in the CBT group versus 54.2 % in the chemotherapy group at 6 months, 61.1 % versus 12.5 % at 12 months, and 38.9 % versus 4.2 % at 18 months. The disease control rate was 68.0 % in the CBT group and 29.8 % in the chemotherapy group (p < 0.001). These results from this retrospective analysis appeared to imply that CBT might prolong survival in these high-risk PC patients. Prospective study is needed to corroborate this observation.
Phase I Trial of Intravenous Thymidine and Carboplatin in Patients With Advanced Cancer
Authors: H. Ian Robins, Kendra Tutsch, Doerthe M. Katschinski, Elaine Jacobson, Minesh Mehta, Mark Olsen, Justin D. Cohen, Cynthia L. Tiggelaar, Rhoda Z. Arzoomanian, Dona Alberti, Chris Feierabend, George Wilding
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the biologic interactions and toxicities of carboplatin combined with a 24-hour infusion of thymidine 75 mg/m 2 in a phase I trial. PATIENTS AND METHODS: Thirty-two patients with cancer refractory to conventional therapy were treated. The first set of patients (n = 7) received thymidine alone 4 weeks before subsequent planned courses of thymidine combined with carboplatin followed (4 weeks) by carboplatin alone. Carboplatin was administered over 20 minutes at hour 20 of the 24-hour thymidine infusion. The carboplatin dose was escalated in patient groups: 200 mg/m 2 (n = 3); 300 mg/m 2 (n = 7); 350 mg/m 2 (n = 4); 400 mg/m 2 (n = 3); 480 mg/m 2 (n = 10); and 576 mg/m 2 (n = 5). At the maximum-tolerated dose (480 mg/m 2 ), five patients received combined therapy first and carboplatin alone second, and five patients received carboplatin first and combined therapy second. Maintenance therapy for stable or responding patients was combined therapy. RESULTS: Evaluation demonstrated a trend toward thymidine protection of carboplatin-induced treatment-limiting thrombocytopenia. Neutropenia with carboplatin alone or in combination was negligible. Thymidine alone had no myelosuppressive effects and produced reversible grade 1 or 2 nausea and vomiting (57%), headache (25%), and grade 1 neurotoxicity (22%). Thymidine did not enhance expected carboplatin toxicities. There was no therapy-related infection or bleeding. Analysis of platinum in plasma ultrafiltrate and urine showed no effect by thymidine. Similarly, thymidine pharmacokinetics was not affected by carboplatin. As predicted, nicotinamide adenine dinucleotide levels in peripheral lymphocytes were increased during exposure to carboplatin and/or thymidine but were decreased by carboplatin alone. In three patients with high-grade glioma, responses included one complete remission (21 months) and one partial remission (14 months) at the 480-mg/m 2 -dose level, and disease stabilization (7 months) at the 400-mg/m 2-dose level. A minor response was observed in a patient with metastatic colon cancer (5 months) at the 480-mg/m 2 -dose level. CONCLUSION: The combination of carboplatin and thymidine as described is well tolerated. The data presented have resulted in a phase II study by the North American Brain Tumor Consortium.
A multicenter study of optical coherence tomography for diagnosis and guided surgery of bladder cancer
Authors: E. Zagaynova, M. J. Manyak, O. Streltsova, N. Gladkova, F. Feldchtein, V. Kamensky
Journal: Journal of Clinical Oncology (2004)

4538 Background: Optical coherence tomography (OCT) is a new biotissue imaging technique with spatial resolution approaching cellular level (10 to 15 μm). OCT can acquire real time in vivo structural images at a depth up to 2 mm. This multicenter study assessed OCT endoscopic diagnostic accuracy for suspicious bladder mucosal and subepithelial areas and for intraoperative adequate resection at tumor borders. Methods: A total of 102 patients were evaluated with 3 scans at each site with images compared to histopathology. Prospective analysis was performed in 95 patients (Group 1) undergoing cystoscopy and retrospective analysis in 7 patients with suspicious lesions (Group 2). Biopsies were obtained in normal and suspicious areas. OCT evaluated tumor borders during partial cystectomy or transurethral resection in 31 patients. Results: In Group 1, 63 of 95 had abnormal areas (31 benign, 32 dysplastic/malignant) with sensitivity of 98%, specificity 72%, positive predictive value (PPV) 78% and negative predictive value (NPV) 98%. In Group 2 with known lesions, sensitivity was 86%, specificity 90%, PPV 75% and NPV 95%. Histological comparison of tumor borders in 50 patients with abnormal scans revealed a 74% confirmation of results with 26% having border extension by OCT due to inflammation. In 6 cases (12%) OCT and the histological tumor extent was found more than 2 cm farther than visual border. No cancer recurrence has been found in 31 of 32 patients in Group 1 with minimal follow up of 15 months. Conclusions: This study suggests that OCT is a promising technology to evaluate bladder lesions found during cystoscopy and tumor extent during resection. High sensitivity and specificity with strong interobserver agreement on OCT strongly supports further evaluation of this as an adjunct to standard evaluation in selected cases. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Imalux Corp. Imalux Corp Imalux Corp. Imalux Corporation
Abstract 2: PTEN Inhibition Improves Cardiovascular Function and Energy Metabolism While Decreasing Inflammation After Mouse Cardiac Arrest
Authors: Jing Li, Huashan Wang, Zuohui Shao, Xiangdong Zhu, Sy-Jou Chen, Changqing Li, Benjamin Steinhorn, Qiang Zhong, James Costakis, Gabrielle Bunney, David Beiser, Terry L Vanden Hoek
Journal: Circulation (2013)

Introduction: The survival kinase Akt mediates therapeutic hypothermia protection after mouse cardiac arrest (CA). This central kinase affects cardiovascular function, metabolism and inflammation. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a primary phosphatase that negatively regulates Akt activity. We hypothesized that the PTEN inhibitor, VO-OHpic (VO), will mimic hypothermia protection by enhancing energy metabolism and cardiac function while reducing inflammation after CA. Methods: C57BL6 mice underwent 8 min of KCl-induced (0.08 mg/g) asystolic CA. VO (10 μg/kg) was administrated IP 30 min before CA. Neurologically intact survival at 72 h after CPR was measured and cardiac function was evaluated by Millar catheter. Blood lactate and glucose were assessed using colorimetric kits, and a cytokine panel using multiplex ELISA. Phosphorylation of Akt, GSK3β and phospholamban in heart and brain were studied by Western blot as markers of Akt activation. Heart cells isolated from 1-2-day old C57BL6 mice and exposed to 30 min ischemia and 90 min reperfusion were used to measure VO effects on contractile function in a cell model of cardiac stunning. Results: VO improved 72 hour survival (90% vs. 50%, p &lt; 0.01). At 30 min after ROSC, VO significantly increased Dp/dt max (5123.4 ± 1026.9 mmHg/s vs. 4033.5 ± 622.4 mmHg/s, p&lt;0.05), and ETCO2 (39.1 ± 2.8 vs. 35.3 ± 1.2 mmHg, p&lt;0.05) with continued benefit seen at 2 hours. VO significantly increased lactate clearance by 4 hours demonstrated by decreased plasma lactate and glucose. The anti-inflammatory cytokine IL10 was increased while VO decreased the pro-inflammatory IL-1β. VO increased the phosphorylation of Akt (Thr308 and Ser473), p-GSK3β and the Akt target phospholamban. In mouse cardiomyocytes, VO (1 μM) improved the contractile velocity (54.6 ± 2.3 % vs. 33.3 ± 3.9 %, p &lt; 0.05), increased total ATP content and the ratio of ATP/ADP during ischemia and enhanced L-type calcium channel recovery. Conclusions: PTEN inhibition improved neurologically intact survival after CA, with improved energy metabolism and cardiac function, and decreased inflammation. Use of PTEN inhibitors such as VO may be a novel strategy with or without cooling for treating the metabolic phase of cardiac arrest.
A multifactorial analysis of prognostic factors in patients with liver metastases from colorectal carcinoma.
Authors: C J Lahr, S J Soong, G Cloud, J W Smith, M M Urist, C M Balch
Journal: Journal of Clinical Oncology (1983)

A multifactorial analysis was used to identify the dominant prognostic variables predicting survival rates of 175 patients with hepatic metastases from colorectal carcinoma. Seven of 22 parameters examined simultaneously were found to independently influence the median survival rate in these patients: (1) elevated alkaline phosphatase (p = 0.0004), (2) elevated serum bilirubin level (p = 0.0005), (3) location of hepatic metastases (unilateral or bilateral, p = 0.0022), (4) number of metastatic nodes involved (0, 1-5, greater than 5; p = 0.0148), (5) depressed serum albumin (p = 0.0217), (6) whether or not the primary colorectal tumor was resected (p = 0.0013), and (7) chemotherapy (given or withheld, p = 0.0439). The prothrombin time, serum lactic dehydrogenase, and the number of hepatic metastases also correlated with survival, but they did not independently predict survival rates after other more dominant factors were accounted for. A mathematical equation for predicting an individual patient's clinical course once they developed hepatic metastases was derived from this statistical analysis. In addition, a simple and clinically useful guide for predicting outcome was developed that integrated the two most important risk factors, alkaline phosphatase and bilirubin.
Diagnostic value of mediastinoscopic biopsy on R4 lymph-node in patients with lung cancer
Authors: J. Liu, J. Wang
Journal: Journal of Clinical Oncology (2005)

7335 Background: Diagnosis of malignant cells in mediastinum lymphnode is important for staging procedures and resulting therapeutic decisions. The aim of this study was to evaluate the application of mediastinoscopic biopsy on right lower trachea-bronchial (R4) lymph-node in diagnosis and pathologic staging on lung cancer. Methods: Sixty-six patients with lung cancer including 47 cases of right lung cancer and 19 cases of left lung cancer received mediastinoscopic biopsy on R4 lymph-node from November 1999 to May 2004. The preoperative diagnosed and suspected lung cancers were 17 and 49 cases, respectively. The operation included cervical mediastinalscopy in 62 cases, parasternal mediastinalscopy in 1 case and cervical combined with parasternal mediastinalscopy in 3 cases. Results: In total 66 patients, Tumor metastases in R4 lymph-node were found in 49 cases. 38 out of 47 patients with right lung cancer and 11 out of 19 patients with left lung cancer were found tumor metastasis in R4 lymph-node. The metastasis rate in small cell lung cancer, adenocarcinoma and squamous cell carcinoma were 100%, 82.2% and 52%, respectively. For diagnosis of the 49 preoperatively suspected lung cancer patients, malignant tumor was confirmed by mediastinoscopic biopsy or open thoracic surgery in 40 and 9 cases respectively. All the operations were successful and the patients recovered smoothly without severe postoperative complications. Conclusions: R4 lymph-node is one of the most common and important site for the tumor metastasis in lung cancer. Mediastinoscopic biopsy on R4 lymph-node has incomparable advantages in diagnosis and staging on lung cancer over other examinations and biopsy on other lymph-nodes. No significant financial relationships to disclose.
Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections
Authors: C. Hauck, E. Cober, S.S. Richter, F. Perez, R.A. Salata, R.C. Kalayjian, R.R. Watkins, N.M. Scalera, Y. Doi, K.S. Kaye, S. Evans, V.G. Fowler, R.A. Bonomo, D. van Duin
Journal: Clinical Microbiology and Infection (2016)