tbuckley/cabot-search huggingface dataset:
Local tumor control and survival outcomes of percutaneous radiofrequency ablation plus post-ablation chemotherapy for lung tumors in nonsurgical patients: A meta-analysis.
Authors: Peter Andrew, Sandra Jerat, Mario Valdes, Richard M. Lee-Ying, Stephen O'Connor
Journal: Journal of Clinical Oncology (2013)

9550 Background: Local recurrence is a frequent outcome post radiofrequency ablation (RFA) for local control of lung tumors. We sought to examine local tumor control and survival benefits of RFA plus post-ablation chemotherapy versus RFA alone for management of lung tumors in non-surgical patients. Methods: Search strategy: MEDLINE, the Cochrane Library, and EMBASE databases from January 2000 to December 2012. Inclusion criteria: RFA +/- post-ablation chemotherapy in non-surgical patients with solid lung tumors. Exclusion criteria: Post-RFA radiation therapy, biologics, brachytherapy, or other ablation modalities. Outcomes: Local tumor progression (LTP), overall survival (OS), and disease-free survival (DFS) at 12 month follow-up. Statistical analysis: Fixed effect analyses, bias assessment, and sensitivity analyses (BioStat Inc., NJ, USA). Results: RFA plus post-ablation chemotherapy group: 11 clinical studies, 684 patients (mean age 64 years [range 50 to 74]; 434 men, ECOG ≤2), ablation of 1,314 lung tumors, with a 4:1 ratio being &lt;3cm versus ≥3cm in diameter, and a 1:4 ratio being primary versus metastatic. RFA alone group: 38 clinical studies, 1,874 patients (mean age 65 years [range 49 to 75]; 1,041 men, ECOG ≤2), ablation of 2,604 lung tumors, with a 2.1:1 ratio being &lt;3cm versus ≥3cm in diameter, and a 1:1 ratio being primary versus metastatic. RFA plus post-ablation chemotherapy versus RFA alone: LTP of 15% over median follow-up of 31 months [range 12 to 59]) versus 19% over median follow-up of 21 months [range 12 to 29]); OR 0.73 (95% CI: 0.61-0.86, p&lt;0.05) at 12 month follow-up. OS was 89% versus 78%, respectively, at 12 month follow-up; OR 1.52 (95% CI: 1.16-2.00, p=0.003). DFS was 90% versus 82%, respectively, at 12 month follow-up; OR 3.18 (95% CI: 2.04-4.96, p&lt;0.05). Sensitivity analyses were robust, publication bias relatively narrow, and heterogeneity within acceptable limits; Q statistic&lt;21; p&gt;0.13 for all outcomes. Conclusions: This meta-analysis reveals that RFA plus post-ablation chemotherapy of lung tumors yields improved outcomes in terms of LTP, OS, and DFS compared with RFA alone.
Abstract 1001: Functional and mechanistic interrogation of androgen receptor degraders for the treatment of metastatic castration resistant prostate cancer
Authors: Steven Kregel, Chao Wang, Ester Fernandez-Salas, Kari Wilder-Romans, Xin Han, Chong Qin, Weiguo Xiang, Jean Tien, Xuhong Cao, Corey Speers, Shaomeng Wang, Arul M. Chinnaiyan
Journal: Cancer Research (2019)

Abstract The clinical development of second-generation androgen receptor (AR) antagonists, including enzalutamide, has confirmed that the AR remains a key oncogene in castration-resistant prostate cancer (CRPC). However, response to enzalutamide is temporary and incremental, and prostate cancer (PCa) cells usually maintain AR expression and signaling upon resistance to AR-targeted therapies. One novel strategy for targeting the AR axis in CRPC is to target proteins through proteasomal degradation, which improves the efficacy and specificity of standard inhibitors. We have developed compounds that bind to AR and engage the proteasomal degradation machinery to specifically degrade the AR protein. Based on this, we hypothesized that the pharmacologic degradation of AR represents an important advance in CRPC treatment, and may provide a novel therapeutic strategy for advanced prostate cancer. These compounds affect AR-positive prostate cancer cells by decreasing AR protein levels as well as disrupting oncogenic AR signaling and enzalutamide resistance. Nanomolar concentrations of AR degraders ultimately lead to decreases in PCa cell growth in vitro and in vivo. In conclusion, we developed highly potent small molecules that induced proteasomal degradation of AR proteins, thus demonstrating degrader compounds to be a potential therapeutic strategy for patients with CRPC. Citation Format: Steven Kregel, Chao Wang, Ester Fernandez-Salas, Kari Wilder-Romans, Xin Han, Chong Qin, Weiguo Xiang, Jean Tien, Xuhong Cao, Corey Speers, Shaomeng Wang, Arul M. Chinnaiyan. Functional and mechanistic interrogation of androgen receptor degraders for the treatment of metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1001.
Interim Results of the Canadian Tyrosine Kinase Inhibitor Discontinuation Trial for 2nd Attempt of Treatment Free Remission: Treatment Free Remission Accomplished By Dasatinib (TRAD)
Authors: Dennis Kim, Isabelle Bence-Bruckler, Donna L Forrest, Lynn Savoie, Stephen Couban, Lambert Busque, Robert Delage, Pierre Laneuville, Elena Liew, Anargyros Xenocostas, Kristjan Paulson, Suzanne Kamel-Reid, Jeffrey H. Lipton, Brian Leber
Journal: Blood (2017)
CD45+CD326+ Cells are Predictive of Poor Prognosis in Non–Small Cell Lung Cancer Patients
Authors: Kota Ishizawa, Mie Yamanaka, Yuriko Saiki, Eisaku Miyauchi, Shinichi Fukushige, Tetsuya Akaishi, Atsuko Asao, Takahiro Mimori, Ryota Saito, Yutaka Tojo, Riu Yamashita, Michiaki Abe, Akira Sakurada, Nhu-An Pham, Ming Li, Yoshinori Okada, Tadashi Ishii, Naoto Ishii, Seiichi Kobayashi, Masao Nagasaki, Masakazu Ichinose, Ming-Sound Tsao, Akira Horii
Journal: Clinical Cancer Research (2019)

The epithelial-to-mesenchymal transition, the major process by which some cancer cells convert from an epithelial phenotype to a mesenchymal one, has been suggested to drive chemo-resistance and/or metastasis in patients with cancer. However, only a few studies have demonstrated the presence of CD45/CD326 doubly-positive cells (CD45/CD326 DPC) in cancer. We deployed a combination of cell surface markers to elucidate the phenotypic heterogeneity in non-small cell lung cancer (NSCLC) cells and identified a new subpopulation that is doubly-positive for epithelial and non-epithelial cell-surface markers in both NSCLC cells and patients' malignant pleural effusions.We procured a total of 39 patients' samples, solid fresh lung cancer tissues from 21 patients and malignant pleural effusion samples from 18 others, and used FACS and fluorescence microscopy to check their surface markers. We also examined the EGFR mutations in patients with known acquired EGFR mutations.Our data revealed that 0.4% to 17.9% of the solid tumor tissue cells and a higher percentage of malignant pleural effusion cells harbored CD45/CD326 DPC expressing both epithelial and nonepithelial surface markers. We selected 3 EGFR mutation patients and genetically confirmed that the newly identified cell population really originated from cancer cells. We also found that higher proportions of CD45/CD326 DPC are significantly associated with poor prognosis.In conclusion, varying percentages of CD45/CD326 DPC exist in both solid cancer tissue and malignant pleural effusion in patients with NSCLC. This CD45/CD326 doubly-positive subpopulation can be an important key to clinical management of patients with NSCLC.
<i>Candida auris</i>in a U.S. Patient with Carbapenemase-Producing Organisms and Recent Hospitalization in Kenya
Authors: Richard B. Brooks, Maroya Walters, Kaitlin Forsberg, Elisabeth Vaeth, Kate Woodworth, Snigdha Vallabhaneni
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Candida auris is an emerging drug-resistant yeast that causes outbreaks in health care facilities; cases have been reported from approximately 30 countries. U.S. cases of C. auris are likely the result of importation from abroad followed by extensive local transmission in health care settings (1). Early detection of Candida auris is key to preventing its spread. C. auris frequently co-occurs with carbapenemase-producing organisms (CPOs), like carbapenem-resistant Enterobacteriaceae (CRE), organisms for which testing and public health response capacity substantially increased beginning in 2017. In September 2018, the Maryland Department of Health (MDH) was notified of a hospitalized resident with CPO infection and colonization and recent hospitalization in Kenya. In light of this history, the patient was screened for C. auris and found to be colonized. Public health responses to CPOs can aid in the early identification of C. auris. As part of CPO investigations, health departments should assess whether the patient has risk factors for C. auris and ensure that patients at risk are tested promptly.
Association of extreme age with worse survival in advanced breast cancer.
Authors: Gema Pulido, Juan de la Haba-Rodriguez, M.Auxiliadora Gomez, Jeronimo Jimenez, Maria Teresa Cano, Maria Jose Ortiz, Enrique Aranda
Journal: Journal of Clinical Oncology (2013)

e11530 Background: Age has been associated with survival in advance breast cancer. In the ALAMO Register prognostic index, older age was associated with mortality. Although recent reports suggest that age below 35 was also associated with worse prognosis. We analysed the impact of extreme ages in survival in an advance breast cancer cohort. Methods: Survival analysis of patients followed in the Advance Breast Cancer Cohort at the Reina Sofia Hospital between 1996-2006. Patients were classified in 4 groups of age: I (&lt; 35), II (35-50), III (51-75) and IV (&gt;75 years). Log-rank test was used to compare survivals between groups. Cases were censored after 5 years of follow-up. A uni and multivariate stepwise regression model was used to estimate factors associated with survival. Results: 212 cases of advance breast cancer were included. Patients’ main characteristics, distributed by age groups, are reported in the Table. Median (IQR) survival was shorter (p=0.01) in group I 12.4 (4.7-25.4) and group IV 10.8 (5.1-19.8) compared to groups II 23.5 (17-29.5) and group III 20.2 (15.2-23.7). Factors independently associated with survival were age groups 1-4 versus 2-3 (p=0.02), histologic grade II-II versus I-unknown (&lt;0.01), disease free interval &lt;24 months versus &gt;24 months (p&lt;0.01) and visceral versus non-visceral metastatic location (p&lt;0.01). Conclusions: Extreme ages (&lt;35 or &gt;75 years) at the diagnosis of the advance breast cancer are associated with worse survival. This factor in addition with the histologic grades, the disease free interval and metastatic location were associated with survival. [Table: see text]
A Fatty Acid Oxidation-dependent Metabolic Shift Regulates the Adaptation of <i>BRAF</i>-mutated Melanoma to MAPK Inhibitors
Authors: Andrea Aloia, Daniela Müllhaupt, Christophe D. Chabbert, Tanja Eberhart, Stefanie Flückiger-Mangual, Ana Vukolic, Ossia Eichhoff, Anja Irmisch, Leila T. Alexander, Ernesto Scibona, Dennie T. Frederick, Benchun Miao, Tian Tian, Chaoran Cheng, Lawrence N. Kwong, Zhi Wei, Ryan J. Sullivan, Genevieve M. Boland, Meenhard Herlyn, Keith T. Flaherty, Nicola Zamboni, Reinhard Dummer, Gao Zhang, Mitchell P. Levesque, Wilhelm Krek, Werner J. Kovacs
Journal: Clinical Cancer Research (2019)

Treatment of BRAFV600E -mutant melanomas with MAPK inhibitors (MAPKi) results in significant tumor regression, but acquired resistance is pervasive. To understand nonmutational mechanisms underlying the adaptation to MAPKi and to identify novel vulnerabilities of melanomas treated with MAPKi, we focused on the initial response phase during treatment with MAPKi.By screening proteins expressed on the cell surface of melanoma cells, we identified the fatty acid transporter CD36 as the most consistently upregulated protein upon short-term treatment with MAPKi. We further investigated the effects of MAPKi on fatty acid metabolism using in vitro and in vivo models and analyzing patients' pre- and on-treatment tumor specimens.Melanoma cells treated with MAPKi displayed increased levels of CD36 and of PPARα-mediated and carnitine palmitoyltransferase 1A (CPT1A)-dependent fatty acid oxidation (FAO). While CD36 is a useful marker of melanoma cells during adaptation and drug-tolerant phases, the upregulation of CD36 is not functionally involved in FAO changes that characterize MAPKi-treated cells. Increased FAO is required for BRAFV600E -mutant melanoma cells to survive under the MAPKi-induced metabolic stress prior to acquiring drug resistance. The upfront and concomitant inhibition of FAO, glycolysis, and MAPK synergistically inhibits tumor cell growth in vitro and in vivo.Thus, we identified a clinically relevant therapeutic approach that has the potential to improve initial responses and to delay acquired drug resistance of BRAFV600E -mutant melanoma.
The role of c-Met inhibition for neuroblastoma treatment.
Authors: Peter Zage, Kathy Scorsone, Linna Zhang
Journal: Journal of Clinical Oncology (2013)

10041 Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood. Many children present with high-risk disease characterized by rapid tumor growth, resistance to chemotherapy, and widespread metastasis, and novel therapies are needed. Previous studies have identified a role for the HGF/c-Met pathway in the pathogenesis of neuroblastoma. We hypothesized that EMD1214063 would be effective against neuroblastoma tumor cells and tumors in preclinical models via inhibition of HGF/c-Met signaling. Methods: We determined the expression of c-Met in a panel of neuroblastoma tumor cells and neuroblastoma cell viability after treatment with EMD1214063 using MTT assays. Analyses were performed for changes in cell morphology, cell cycle progression, and cell death via apoptosis after EMD1214063 treatment. To investigate the efficacy of EMD1214063 against neuroblastoma tumors in vivo, neuroblastoma cells were injected orthotopically into immunocompromised mice, and the mice in which tumors developed were treated with oral EMD1214063. Results: All neuroblastoma cell lines were sensitive to EMD1214063, and IC50 values ranged from 2.4 - 8.5 mcM. EMD1214063 treatment inhibited HGF-mediated c-Met phosphorylation in neuroblastoma cells. EMD1214063 induced cell cycle arrest in neuroblastoma tumor cells with high c-Met expression, and induced apoptosis in all tested cell lines. In mice with neuroblastoma xenograft tumors, EMD1214063 inhibited tumor growth. Conclusions: Treatment of neuroblastoma tumor cells with EMD1214063 inhibits HGF-induced c-Met phosphorylation and results in cell death. Furthermore, EMD1214063 induces cell cycle arrrest prior to cell death in neuroblastoma tumor cells with high c-Met expression. EMD1214063 treatment is effective in reducing tumor growth in vivo in mice. Inhibition of c-Met represents a potential new therapeutic strategy for neuroblastoma, and further preclinical studies of EMD1214063 are warranted.
The predictive value of hENT 1 molecule for gemcitabine treatment in bladder cancer.
Authors: Didem Sener Dede, Aydan Kilicaslan, Muhammed Bulent Akinci, Umut Demirci, Gozde Tahtaci, Bulent Yalcin
Journal: Journal of Clinical Oncology (2013)

e15540 Background: Human equilibrative nucleoside transporter 1 (hENT1) is the nucleoside transporter protein which plays the main role for transportation of gemcitabine into the cells. We aim to assess the predictive value of the hENT 1 molecule in bladder cancer patients treated with gemcitabine based chemoterapy. Methods: Clinically and histologically documented stage III and stage IV invazive bladder cancer patients were included in the study. The patients were assessed retrospectively. All patients were received gemsitabine-platine based chemotherapy as the first line treatment. Spesific hENT1 antibody staining was performed on the chemo-naive bladder tumor specimens immunuhistochemically. Vascular endotel and lymphocytes served as an external positive control for hENT 1 immunuhistochemistry. Staining intensity was graded as 0,absent; 1+, less intens than control tissue, 2, equally positive as control tissue; 3, more intense than control tissue. Tumor spesimens with having 3+ intensity staining in &gt;50% of the tumor cells were accepted as showing high expression of hENT 1. Results: Fifty one patients were included in the study. The median age was 67 (range 41-85). Ninety two percent(n=52) of patients were male. Twenty six (46.4%) and 25 (44.6%) patients were stage III and stage IV disease at the beginning of the therapy, respectively. Thirty four (60.7%) patients were in neoadjuvant treatment group and 17 (30.4%) patients were in metastatic group. Tumor grades could be assessed in 33 patients; 2 (11.4%) were low grade and 31 (88%) were high grade. The median folllow up period was 13 (range 1-58) months. In neoadjuvant group 5 (14%) patients have low hENT 1 level and 21 (60%) patients have high hENT 1 level. In metastatic group 1 (5%) patients have low hENT1 level and 13 (95%) patients have high hENT 1 level. We found no statistically significant difference between hENT 1 low and hENT 1 high groups in terms of response to therapy in metastatic and neoadjuvant groups (p=0.426 and p=0.684 respectively). Conclusions: More stuides are needed to demonstrate the real role of hENT 1 molecule in terms of response to gemsitabine treatment.
B Cell–Adaptive Immune Profile in Emphysema-Predominant Chronic Obstructive Pulmonary Disease
Authors: John-Lawrence Sullivan, Bhavani Bagevalu, Carolyn Glass, Lynette Sholl, Monica Kraft, Fernando D. Martinez, Gorka Bastarrika, Juan P. de-Torres, Raul San Jose Estepar, Stefano Guerra, Francesca Polverino
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Moderate-to-severe symptoms among survivors of early-stage breast cancer.
Authors: Helene B. Zonder, Joanne E. Mortimer, Carolyn E. Behrendt, Robin Smith, Meghan Zomorodi
Journal: Journal of Clinical Oncology (2012)

e19644 Background: This cross-sectional survey describes the prevalence of moderate/severe symptoms among patients in a survivorship clinic. Methods: We administered QoL questionnaires (FACT-B, SF-36, HADS) to pts. treated for stage I-III disease at a survivorship visit. For symptoms reported by at least 18/55 subjects, we identified risk factors using logistic regression. Results: Subjects (n=55) were age 55.9(+8.9) yrs at study, age 52.6(+9.3) at dx, and median 23.7 (range 6.3-157.2) mos. from dx of stage I (30.9%), II (54.5%), or III (14.6%) disease. Systemic treatment included chemotherapy only (20.0%), endocrine therapy only (30.9%), or both therapies (49.1%). Currently, 65.5% were on endocrine therapy. Symptoms experienced “quite a bit” or “very much” during the past wk were: hot flashes (45.5%), joint pain (30.9%), weight gain (30.9%), loss of libido (30.9%), vaginal dryness (27.3%), and night sweats (27.3%). In the past mo., 43.6% accomplished less than they would have liked due to physical health, and 30.9% felt worn out at least “a good bit of the time”. Sleep quality was rated “fairly to very bad” (32.7%), and 25.5% felt fatigued at least half the day during the past week. Vigorous activities were “limited a lot” for 36.4%, and increased with age at dx. Fre-quent hot flashes were associated with age &lt; 50 years (6.40, 1.75-23.35) and being within 1year of dx (10.67, 1.05-108.69). Adjusted for age at dx, poor quality of sleep increased with stage of disease (9.68, 2.25-41.69, per step increase) and was associated with having received endocrine therapy only (9.98, 1.40-71.03) and being within the first year after dx (9.54, 0.76-119.47). Conclusions: Limitation in activities, poor quality of sleep, and symptoms of hormonal suppression are common among survivors of early stage breast cancer. Poor quality sleep and frequent hot flashes appear to decrease in prevalence 1 yr after dx, but other common symptoms do not. A longitudinal cohort study is underway.
Uroporphyrinogen decarboxylase gene expression in oral squamous cell carcinomas.
Authors: Rajkumar Kottayasamy Seenivasagam, Arun Kumar Ganesan, Rajaraman Ramamurthy, Munirajan Arasambattu Kannan, Deva Magendhra Rao
Journal: Journal of Clinical Oncology (2013)

e17002 Background: Oral cancer is one of the most common cancers in India. Uroporphyrinogen decarboxylase (UROD), a key regulator of heme biosynthesis, has recently been suggested as a novel tumor-selective radiosensitizing target against head and neck cancers. Further, a recent study has suggested that tumors with UROD expression may have poorer outcomes and higher rates of recurrence. We tested the expression of UROD splice variants in oral cancer patients who were treated in our hospital to study its expression and impact on the patients. Methods: The expression of both coding and noncoding splice variants of UROD gene was tested in 42 patients (31 male, 11 female) with oral cavity squamous cell carcinomas treated in 2011-12. Pretreatment tumor biopsies were collected and mRNA was extracted using Quiagen RNeasy kit method. cDNA was synthesized using Superscript III and subjected for UROD expression using specific primers. UROD expression and clinical data of patients were analyzed using IBM SPSS 20 Software. Results: The mean age of the patients was 52 years (range 32-70). Buccal mucosa (n=17) and tongue (n=13) were the most common subsites. Seventy six percent had locally advanced disease (T3/T4 and node-positive) and high-grade (70%) cancers. Chemoradiotherapy (CRT) (n =25) and chemotherapy (CT) (n = 10) was given in 35 patients of which 5 had progressive disease. The mean follow up was 11 months. Thirty seven patients were operated, 5 developed locoregional recurrence and 2 developed spine metastases and died during follow-up. UROD was expressed in 23 (54.8%) patients (coding variant = 52.8%, noncoding = 26%). There was no correlation between UROD expression and age, sex, subsite, stage, grade or node positivity. Patients with UROD expression had a slightly poorer response to CRT/CT (30.4% vs 24.1%; p =NS). Similarly, though they had a slightly higher incidence of recurrence, the difference was not significant. Both patients with spinal recurrence had UROD expression. Conclusions: UROD is highly expressed in oral cancer patients in India. Its proposed radiosensitizing and prognostic role in treatment and outcomes though promising needs further evaluation in a larger number of patients.