tbuckley/cabot-search huggingface dataset:
A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in patients with metastatic or recurrent esophageal squamous cell carcinoma.
Authors: Shuji Hiramoto, Ken Kato, Hirokazu Shoji, Natsuko T. Okita, Atsuo Takashima, Yoshitaka Honma, Satoru Iwasa, Tetsuya Hamaguchi, Yasuhide Yamada, Yasuhiro Shimada
Journal: Journal of Clinical Oncology (2015)

204 Background: Patients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, 5-fluorouracil /Cisplatin (FP) have been mostly used for these patients as first line chemotherapy. But there were few reports which reveal the reality containing the efficacy of FP regimen for ESCC. We conduct this retrospective study to reveal the efficacy and prognostic factors of the patients treated with FP as first line chemotherapy for ESCC. Methods: Patients with metastatic or recurrent ESCC after esophagectomy were enrolled. FP comprised of CDDP at a dose of 80mg/m 2 on day1, and 5-FU at a dose of 800mg/m 2 given by continuous on days 1-5 every 4 weeks. Cox-proportional hazard model was used for multivariate analysis to evaluate prognostic factors. Results: Between April 2001 and March 2012 in the National Cancer Center Hospital, data of 187 patients were collected by medical records. Characteristics of 187 patients were as follows; the median age (range) 62 (34-84); (male/female) 163/24; (performance status: 0/1/2) 69/110/8; (metastatic/recurrent) 116/71; median number of metastasis 1(range1-4); median cycles of FP 2(range1-10). Overall response rate was 31.6% (95%CI: 25.0-38.7%). Median progression free and overall survival time was 4.9 month and 10.5 month, respectively. In multivariate analysis, serum CRP (≥2 vs &lt;2 mg/dl) (HR=2.61, p&lt;0.001), serum albumin (&lt;3.5 vs &gt;3.5 mg/dl) (HR=1.85, p=0.001) at the time of diagnosis and number of metastatic site (≥2 vs &lt;2) (HR=1.563, p=0.01) were remaining independent prognostic factor for survival. Survival time of the patients who had no these poor prognostic factors was 17.9 month, while survival time who had all poor prognostic factors was only 4.0 month. Conclusions: Number of metastatic site, CRP, and serum albumin are independent prognostic factor on metastatic or recurrent ESCC patients treated with FP. Information from this analysis can be used to aid clinical decision-making and help individual patient risk stratification.
A phase II noncomparative study of neoadjuvant (NA) chemohormone therapy (CHT), radical prostatectomy (RP), and postoperative radiotherapy (RT) in locally advanced (LA) high-risk prostate cancer (HRPC): A monoinstitutional 6-year experience with two NA CHT regimens
Authors: G. Lo Re, M. Boccalon, D. Maruzzi, R. Bortolus, O. Lenardon, V. Marus, C. Rustici, S. Tumolo, A. Garbeglio, S. Sulfaro
Journal: Journal of Clinical Oncology (2009)

e16091 Background: HRPC criteria include stage T2b-T2c according to the AJCC classification, PSA ≥ 10 ng/ml, Gleason score (GS) 7–10 with 12, 6% 7-year cancer specific mortality rate (D'Amico AV, Cancer. 2006). Several small nonrandomized NA chemotherapy studies were performed in this setting (Kim N. Chi J Urol. 2008; Prayer-Galletti T. Br J Urol. 2007; Konety BR. J Urol. 2004) with DFS of 42%-70%. Aim of this study: to evaluate the feasibility, efficacy, and toxicity of NA-CHT followed by RP and postoperative RT. Methods: Histological diagnosis of LA HRPC (T2b-T4), GS &gt; 8, PSA &gt; 10 ng/ml, age &lt; 65 years, PS 0–1. Treatment: group A) paclitaxel 80 mg/sqm/weekly and estramustine phosphate (EP) 10 mg/Kg/day for 5 days/week for 4 months. Group B) carboplatin (AUC 5) i.v day 1 q 21 plus docetaxel 30 mg/sqm i.v day 1,8 and EP day -1-+4 and 7–11 q 21 for 4 cycles. Thereafter, the responsive and stable patients (pts) were submitted to RP and adjuvant RT (60–70Gy/30–35 fr) or to radical (R) RT (78 Gy/39 fr) respectively. Primary endpoint: disease-free survival (DFS); secondary endpoint: PSA relapse-free survival (RFS), overall survival (OS). Results: Between 2002 and 2008, 29 pts entered onto the studies. The toxicity was mild. The down-staging was obtained on 2 group A pts and on 1 group B pt respectively. Conclusions: NA-CHT with both regimens was been shown feasible and nontoxic in LAHRPC. Although a clinical response was documented, the pathological response was anecdotal.The DFS and OS are encouraging considering the historical data but warrant a randomized study. [Table: see text] No significant financial relationships to disclose.
An open-label, randomized, study of h-R3mAb (nimotuzumab) in patients with advanced (stage III or IVa) squamous cell carcinoma of head and neck (SCCHN): Four-year survival results from a phase IIb study.
Authors: K. G. Babu, L. Viswanath, B. K. Reddy, K. Shenoy, A. Shenoy, T. Naveen, B. Joseph, M. S. Vidyasagar, R. Bonanthaya, C. T. Pasha, P P Bapsy, A S Aravind, A Eswaraiah, N Gupta
Journal: Journal of Clinical Oncology (2010)

5530 Background: h-R3mAb (nimotuzumab) is a humanized monoclonal antibody targeting epidermal growth factor receptor (EGFR). EGFR is over-expressed in >90% squamous cell carcinoma of head and neck (SCCHN). Patients with advanced inoperable SCCHN have poor outcome to radiotherapy (RT) or chemoradiotherapy (CRT) treatment alone. Adding biologically active targeted therapies to RT/CRT might further improve therapeutic outcome with minimal morbidity. Methods: Total of 113 patients with (stage III or IVa), inoperable SCCHN were screened; 92 randomized in 1:1 ratio in two groups; group A received [RT Vs RT+h-R3mAb] and group B received [CRT vs. CRT+h-R3mAb]. Treatment included radiotherapy in total dose 60 -66Gy, h-R3mAb 200mg by I.V infusion over 60 min/ week for 6weeks and in group B, chemotherapy CDDP 50mg/week for 6weeks. Results: Seventy-six patients were evaluable; 36-groupA and 40-groupB. Locoregional response was 100% in CRT+h-R3mAb vs. 70% in CRT and 76% in RT+h-R3mAb vs. 37% in RT. At 48 months follow-up; Overall survival rate (ITT) was 47% in (CRT+h- R3mAb) vs. 21% (CRT)(p = 0.01) and 34% (RT+h-R3mAb)vs. 13%(RT)(NS), median overall survival was NR* for (CRT+h-R3mAb) vs. 21.9 months (CRT)(HR-0.35, P-0.01) and 14.3months (RT+h-R3mAb) vs. 12.7months (RT)(HR-0.74, P-0.42). The subjects alive in CRT+h-R3mAb arm had mean EGFR values of 67.5%. There was no statistically significant difference in mean EGFR % with respect to survival of alive and deceased in this population. Adding h-R3mAb to Chemoradiation resulted in significant reduction in risk of death by 65 % (HR 0.35, p-0.01). Conclusions: Concurrent use of h-R3mAb with RT/CRT is safe and efficacious; it enhanced locoregional control and survival on long term follow-up. This is the first randomized study demonstrating clinical benefit from EGFR-targeting mAb in the absence of the advanced toxicities due to its distinguished property of preferentially targeting the tumor. The encouraging efficacy data recommends further development of CRT+h-R3mAb paradigm in treatment of SCCHN. No significant financial relationships to disclose.
Efficacy of RAD001/carboplatin in triple-negative metastatic breast cancer: A phase II study.
Authors: Jasmeet Chadha Singh, Matthew Volm, Yelena Novik, James L. Speyer, Sylvia Adams, Coral Oghenerukevwe Omene, Marleen Iva Meyers, Julia Anne Smith, Robert Schneider, Silvia Formenti, Judith D. Goldberg, Xiaochun Li, Samantha Davis, Brian Beardslee, Amy Tiersten
Journal: Journal of Clinical Oncology (2012)

108 Background: Triple-negative breast cancer cells are unable to repair double stranded DNA breaks and have sensitivity to platinum agents. Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. RAD001 (oral mTOR inhibitor) and Carboplatin combination may have activity in triple-negative breast cancer. Methods: The primary objective is to estimate clinical benefit (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting &gt;6 months) and toxicity of the combination in triple negative metastatic breast cancer patients who have had 0-3 prior chemotherapy regimens. This design has &gt; 80% power to test the null hypothesis i.e. clinical benefit rate is ≤ 10% vs. alternative hypothesis that clinical benefit rate is ≥ 30%. Prior carboplatin is allowed. Women with treated brain metastasis are eligible. Originally, carboplatin AUC 6 was to be administered every 3 weeks along with daily 5mg of RAD001 with a 3 patient run-in and then 10 mg daily. Due to a surprising amount of thrombocytopenia, the dose of carboplatin was first amended to AUC 5 and most recently to AUC 4 with 5 mg of RAD001 (no escalation to 10 mg). Results: 23 out of 25 patients have been recruited. Median age is 59. Thus far, there have been 1 CR, 5 PR’s, 8 SD's and 6 PD’s. One SD was achieved in a patient progressing on single agent carboplatin at study entry. Median duration of response is 13 weeks (range: 6-74 weeks). 5 patients had grade 3/4 thrombocytopenia and 4 patients had grade 3 neutropenia (no febrile neutropenia). 13 patients had treatment held and/or dose reductions secondary to hematological toxicity. Since dosing amendment for carboplatin to AUC 4 the regimen has been well tolerated (only 1 patient with grade 3 neutropenia and thrombocytopenia). 1 patient had grade 3 dehydration. The estimated clinical benefit rate is 45% (95% C.I.: 23%, 67%). Median time to progression or death is 85 days from start of treatment. Conclusions: Our study has met the primary end point of demonstrating clinical benefit in triple-negative metastatic breast cancer. Dose-limiting thrombocytopenia was an unexpected side effect requiring protocol amendment. Patient accrual continues at the amended dosing.
Biologic differences between squamous cell carcinomas and adenocarcinomas of the lung demonstrated by tissue arrays: Interest for the 18F-FDG-PET.
Authors: K. Areses, U. Anido, A. Ruibal, I. Abdulkader, F. Gude, A. Sanchez-Salmon, L. Leon, S. Argibay, J. Forteza, R. Lopez
Journal: Journal of Clinical Oncology (2010)

e21087 Background: To study the possible contribution of some biological factors to explain the higher SUVmax values in 18F-FDG PET detected in squamous cell carcinomas in contrast with those found in non bronchoalveolar adenocarcinomas. Methods: The study group included 139 patients (129 males), median age 64.8 years old (range 41-86) with NSCLC (85 squamous cell and 54 adenocarcinomas) newly diagnosed. Adenocarcionoma: 17 stage I, 2 II, 22 III and 13 IV; Squamous cell: 21 I, 16 II, 33 III and 15 IV._ Immunohistochemical expression of different biological parameters was studied by means of tissue-matrix using Tissue Arrayer Device (Beecher Instruments, Sun Prairie, WI). Positive tumours were classified: + > 10% stained tumour cells, ++ when it ranged between 30-50% and +++ when it was over this value. Results: The squamous cell carcinomas were less frequent in women (2/85 vs 8/54; p: 0,016) and they showed higher expression of bcl-2 (38/85 vs 14/54; p:0.0257), cyclin A (66/85 vs 21/54; p:0,0000), cyclin B1 (74/85 vs 36/54; p:0.0039), cyclin D2 (68/85 vs 20/54; p:0.0000), p21 (82/85 vs 30/54; p:0.0000), p53 (61/85 vs 27/54; p:0.009), p63 (75/85 vs 5/54; p:0.0000), MIB1 (79/85 vs 42/54; p:0.009) and EGFR (56/85 vs 26/54; p:0.030). On the other hand, adenocarcinomas were more frequently COX-2 positive (16/85 vs 20/54; p:0.017). There were no differences in the rest of the parameters measured. These differences (MIB1, EGFR, cyclin B1 and COX-2) might support the idea that the squamous cell carcinomas show higher values of maxSUV concordant with the results described in the literature. We did the follow up of 81 patients during a median time of 21 months (range 1-80) and after multivariate analysis we could observe that only the clinical stage (I-II vs III-IV; p:0.009; HR: 2,45) was an independent outcome factor. Conclusions: 1) the squamous cell carcinomas of the lung have a biological profile different from that of the adenocarcinomas, with higher expression of several parameters, some of them could have any influence in the maxSUV of the 18F-FDG-PET such as MIB1, EGFR, cyclin B1 and COX-2. 2) The clinical stage was the only prognostic factor after a multivariate analysis. No significant financial relationships to disclose.
A phase I study of bexarotene and rosiglitazone in patients with refractory cancers
Authors: W. L. Read, M. Q. Baggstrom, D. Adkins, R. Suresh, R. Ghalie, J. Wildi, R. Govindan
Journal: Journal of Clinical Oncology (2006)

13094 Background: Preclinical studies have shown that ligands of the PPAR-γ receptor can slow growth and promote differentiation of malignant cells. Rosiglitazone is a high affinity PPAR-γ ligand approved for treatment of insulin resistant diabetes. After binding ligand, the PPAR-γ receptor heterodimerizes with the RXR receptor. Bexarotene is an RXR ligand with cytostatic properties similar to those of PPAR-γ agonists. Ligands of RXR and PPAR-γ are synergistic, causing cell differentiation and apoptosis. Methods: We conducted a phase 1 study of bexarotene and rosiglitazone in patients with resistant malignancies to define the MTD of rosiglitazone in this regimen. Patients received bexarotene 300 mg/m 2 daily. The starting dose of rosiglitazone was 4 mg/day. This dose was escalated in five cohorts using the modified Fibonacchi scheme (4–6-8–10–12). Both drugs were continued until disease progression or toxicity. Patients received atorvastatin 10 mg daily, which was increased based on weekly triglyceride levels. Results: We enrolled 23 patients without encountering dose limiting toxicity. After reaching 12 mg/day of rosiglitazone, the study was closed because of laboratory evidence showing no further synergy at higher doses. Patient Characteristics: Histological type: NSCLC 8, sarcoma 3, prostate 2, and others (SCLC, thyroid/breast, mesothelioma, esophageal, breast, colorectal, renal, parotid, transitional cell, cervical). Median cycles of treatment delivered 1 (range 0–4). The primary serious adverse events (grade 3 or 4) were hyperglyceridemia (17%), dyspnea (9%), nausea (9%), dehydration (9%). Two patients expired, both due to disease progression. Responses: CR/PR none, SD 3, disease progression 14, not evaluable 4, patient withdrawal 2. Conclusions: The combination of bexarotene (300 mg/m 2 /day) and rosiglitazone (12 mg/day) is safe and feasible. No responses were seen in this heavily pretreated population, which is not surprising given that both agents are cytostatic, rather than cytotoxic. This combination might be studied in cutaneous T-cell lymphoma, or as adjuvant/maintenance therapy in other malignant diseases. Other areas for study might include inflammatory diseases where PPAR-γ ligands have activity. This study was supported by Ligand pharmaceuticals. [Table: see text]
Abstract 15373: The Clinical and Hemodynamic Characteristics of Transition to Eisenmenger Syndrome in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease: A National Multicenter Study
Authors: Cihangir Kaymaz, Serdar Kucukoglu, Gul Sagin Saylam, Serdar Kula, Dursun Alehan, Lale Tokgozoglu, Atif Akcevin, Alpay Celiker, Sertac Cicek, Kemal Baysal
Journal: Circulation (2012)

Purpose: Although pulmonary arterial hypertension (PAH) associated with congenital heart disease (APAH-CHD) may show a progression to Eisenmenger Syndrome (ES), the clinical and hemodynamic aspects...
The Ubiquitin-Like SUMO System and Heart Function
Authors: Luca Mendler, Thomas Braun, Stefan Müller
Journal: Circulation Research (2016)

SUMOylation is a ubiquitin-related transient posttranslational modification pathway catalyzing the conjugation of small ubiquitin-like modifier (SUMO) proteins (SUMO1, SUMO2, and SUMO3) to lysine residues of proteins. SUMOylation targets a wide variety of cellular regulators and thereby affects a multitude of different cellular processes. SUMO/sentrin-specific proteases are able to remove SUMOs from targets, contributing to a tight control of SUMOylated proteins. Genetic and cell biological experiments indicate a critical role of balanced SUMOylation/deSUMOylation for proper cardiac development, metabolism, and stress adaptation. Here, we review the current knowledge about SUMOylation/deSUMOylation in the heart and provide an integrated picture of cardiac functions of the SUMO system under physiologic or pathologic conditions. We also describe potential therapeutic approaches targeting the SUMO machinery to combat heart disease.
Bringing Biosimilars to the Clinic: What's the Fuss?
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2016)

Dr. Tempero is a Professor of Medicine and Director of the UCSF Pancreas Center, and the editorin-chief of JNCCN. Her research career has focused on pancreatic ductal adenocarcinoma, especially in the area of investigational therapeutics. Dr. Tempero has served on the ASCO Board of Directors and as ASCO President. She co-directed the AACR/ASCO Methods in Clinical Cancer Research and taught this course and similar courses in Europe and Australia. She was founding Chair of the NCI Clinical Oncology Study Section (CONC) and served as a member and chair of the NCI Board of Scientific Counselors Subcommittee A. She is on the External Advisory Boards of the Pancreas SPOREs at Mayo Clinic and at UAB/Minnesota and the GI SPORE at the University of Arizona. She is, or has been, on the Scientific Advisory Boards of the Lustgarten Foundation, the Pancreatic Cancer Action Network, the V Foundation, The Alberta Canada Cancer Board, and the EORTC. She served as a member of the Oncology Drug Advisory Committee for the FDA. She has served as Deputy Director and Interim Director for the UNMC Eppley Cancer Center. She is Chief Emeritus of the Division of Medical Oncology at UCSF and served as Deputy Director and Director of Research Programs at the UCSF Helen Diller Family Comprehensive Cancer Center. Bringing Biosimilars to the Clinic: What’s the Fuss?
Relationship of acute gastrointestinal toxicity and the volume of irradiated small bowel in patients receiving combined modality therapy for rectal cancer.
Authors: B D Minsky, J A Conti, Y Huang, K Knopf
Journal: Journal of Clinical Oncology (1995)

To determine the relationship between acute gastrointestinal (GI) toxicity during the combined modality segment and the volume of small bowel in the pelvic radiation field in patients who receive either preoperative or postoperative therapy for rectal cancer.The patient population was derived from four consecutive phase I dose-escalation trials. Combined modality therapy included fluorouracil (5-FU), leucovorin ([LV] bolus daily x 5, days 1 and 29), and pelvic radiation.Twenty patients who received postoperative therapy had a larger volume of small bowel in the pelvic radiation field as compared with 60 who received preoperative therapy (462 +/- 129 v 212 +/- 44 cm3, P = .002). The most significant relationship between acute GI toxicity and volume of small bowel was seen in 12 patients who were treated on the preoperative sequential low-dose LV trial, all of whom received the maximum-tolerated dose (MTD) of 5-FU. The volume of small bowel in patients who experienced grade 3+ toxicity was 731 +/- 274 cm3, as compared with 145 +/- 58 in those who experienced grade 0 to 2 toxicity (P = .005). Likewise, logistic regression analysis showed that 26 patients who received the MTD of 5-FU had the most significant association between GI toxicity and volume of small bowel (P = .036).Our data suggest that the volume of small bowel in the pelvic radiation field may be dose-limiting in the delivery of high-dose 5-FU when combined with LV and radiation therapy.
Lysyl Oxidase, a Targetable Secreted Molecule Involved in Cancer Metastasis
Authors: Thomas R. Cox, Alison Gartland, Janine T. Erler
Journal: Cancer Research (2016)

Abstract Secondary metastatic cancer remains the single biggest cause of mortality and morbidity across most solid tumors. In breast cancer, 100% of deaths are attributed to metastasis. At present, there are no “cures” for secondary metastatic cancer of any form and there is an urgent unmet clinical need to improve the tools available in our arsenal against this disease, both in terms of treatment, but also prevention. Recently, we showed that hypoxic induction of the extracellular matrix modifying enzyme lysyl oxidase (LOX) correlates with metastatic dissemination to the bone in estrogen receptor negative breast cancer and is essential for the formation of premetastatic osteolytic lesions. We showed that in models of breast cancer metastasis, targeting LOX, or its downstream effects, significantly inhibited premetastatic niche formation and the resulting metastatic burden, offering preclinical validation of this enzyme as a therapeutic target for metastatic breast cancer. Our work is the latest in an emerging body of work supporting the targeting of LOX and calls for greater efforts in developing therapeutics against this extracellular secreted factor in the prevention of cancer progression across multiple solid tumor types. Cancer Res; 76(2); 188–92. ©2016 AACR.
Development of a cell line based gene classifier to predict therapeutic response of head and neck cancer patients
Authors: Seema Gupta, Sana Ghafoor, Craig Wood, Kathryn Masker, Robert Brown, Amy Law, Phillip Pellitteri, Ping Zhang, David Carey, Mansoor Ahmed
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4098 

A major goal of cancer biology is the development of assays to predict therapeutic response in solid tumors. We developed a classifier that predicts clinical response to chemotherapy and radiation therapy of squamous cell carcinomas of the head and neck (SCCHN) based on expression profiles of genes in the NFκB signaling pathway. As a starting point we used two SCCHN tumor cell lines (SQ20B and T409) that were both radio- and chemotherapy resistant and two SCCHN tumor cell lines (SCC61 and T167) cells that were sensitive to these treatments. Isolated mRNA was used to test the expression levels of 84 genes involved in NFκB signaling pathway using real time RT PCR. Eighteen genes showed changes in expression of more than 4-fold in radioresistant cells compared to radiosensitive cells (14 up-regulated and 4 down-regulated). The down-regulated genes included NFκB target genes (ICAM1 and CSF2) and an NFκB signaling activator (IL8). The up-regulated genes included regulators of NFκB signaling (TBK1, HTR2B, BIRC2, and TLR6). A multivariate linear regression model was used to identify gene expression patterns that correlated with response, using radiation or chemotherapy-based cell killing as a continuous variable. This process identified eight NFκB dependent genes with expression levels that correlated with resistance to radiation and chemotherapy. These were used to generate a set of classifier rules to distinguish sensitive from resistant cells. The classifier rules were then validated using primary tumor specimens from 22 untreated SCCHN cancer patients. Expression profiling data obtained using RNA isolated from these tumors were stratified using the classifier rules and the response was predicted. The predicted response was then compared to the actual clinical outcome, defined as tumor recurrence after therapy, using data obtained from electronic health records of the patients. The classifier correctly predicted the clinical response in 90% (20 of 22) of the cases. However, using McNemar's statistical method (p-value=0.001) only 31% of the assayed genes showed concordance in expression pattern between the original cell lines and patient samples. In conclusion, we demonstrate that therapeutic response can be predicted based on gene expression profiles. We did this by identifying novel associations between molecules in the NFκB signaling pathway and treatment sensitivity. The classifier rules we developed correctly predicted clinical outcome in a high percentage of patients, which has significant implications for patient therapy. Analysis of more patient samples as well as other pro-survival signaling pathways is needed before these methods are generally used in the clinic.