tbuckley/cabot-search huggingface dataset:
Role of three axillary lymph node sampling for predicting non-sentinel node metastases in patients with breast cancer and positive sentinel node
Authors: K. Motomura, S. Nagumo, C. Egawa, Y. Komoike, T. Kasugai, Y. Hasegawa, H. Inaji, H. Koyama
Journal: Journal of Clinical Oncology (2004)

694 Background: Half of breast cancer patients with positive sentinel node (SN)s do not have further metastatic non-SNs and do not need to undergo axillary lymph node dissection (ALND). This study evaluated the usefulness of three axillary lymph node (ALN) sampling for predicting non-SN metastases in breast cancer patients with SN metastases. Methods: SN biopsy was performed in patients with clinically node-negative breast cancer using dye and radioisotope. When SNs were diagnosed as metastasis-positive by intraoperative imprint cytology, three ALN sampling was performed, followed by ALND. The metastatic status of sampled nodes was compared with that of non-SNs. Imprint cytological evaluation was also performed for the sampled nodes and was compared with the final histological results of the sampled nodes. Results: Between 2001 and 2003, 252 patients underwent SN biopsy. Of 39 (16%) patients with positive imprint cytology, 36 (14%) were diagnosed as tumor positive on final histological examination and analyzed. The mean patient age was 51 (30–75) years old and the mean tumor size was 18 (8–28) mm. The mean number of SNs was 2.4 (1–7) and the mean number of non-SNs other than sampled nodes was 10.7 (2–27). The sensitivity, specificity and accuracy of sampled nodes for predicting non-SN metastases were 82%, 100% and 94%, respectively (sampled node+/ non-SN+, 9; +/-, 0; -/+, 2; -/-, 25). The negative predictive value and positive predictive value of sampled nodes for predicting the metastatic status of remaining ALNs other than sampled nodes were 93% and 56%, respectively. The sensitivity, specificity and accuracy of imprint cytology for sampled nodes were 86%, 97% and 95%, respectively on a node basis (cytology+/ histology+, 12; +/-, 3; -/+, 2; -/-, 91), and 90%, 96% and 94%, respectively on a patient basis (cytology+/ histology+, 9; +/-, 1; -/+, 1; -/-, 25). Conclusions: Three ALN sampling is useful for predicting non-SN metastases and avoiding ALND in breast cancer patients with SN only metastases. Furthermore, intraoperative imprint cytological examination is useful for detecting metastases in sampled nodes. No significant financial relationships to disclose.
Phase II presurgical study of bevacizumab plus erlotinib in untreated patients with metastatic renal cell carcinoma
Authors: E. Jonasch, D. Tsavachdidou, C. G. Wood, S. F. Matin, P. G. Corn, P. Tamboli, X. Wang, N. Tannir
Journal: Journal of Clinical Oncology (2009)

5004 Background: The safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC) is not known. The current study was designed to answer these clinical questions, and to define predictive tissue biomarkers using nephrectomy specimens from patients on trial. Methods: Patients with newly diagnosed clear cell mRCC whose primary tumor was considered resectable were enrolled. In this single arm phase II trial, patients received bevacizumab plus erlotinib or bevacizumab alone for 8 weeks, followed by restaging. Primary endpoint was progression free survival (PFS). If patients demonstrated progressive disease and had a declining performance status after eight weeks, nephrectomy was deferred. Postoperatively, patients continued on study drug(s) if disease stabilization or regression had occurred. Reverse phase protein arrays (RPPAs) were generated from nephrectomy specimens. Results: Between March 2005 and March 2008, 52 patients were enrolled on the study, and 50 were included in the analysis. By the Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk features. Twenty-three patients received bevacizumab plus erlotinib, and 27 received bevacizumab alone. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI: 5.5, 15.6 months). Median overall survival was 25.4 months (95% CI 11.4, not estimable). Two perioperative deaths occurred, and neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients. RPPA analysis demonstrated a clear separation of better versus worse responding patients. Conclusions: Presurgical treatment with bevacizumab therapy is relatively safe and yields clinical outcomes comparable to post surgical treatment with antivascular therapy in patients with mRCC. Prospective randomized trials testing the use of presurgical therapy to select appropriate patients for cytoreductive nephrectomy are warranted. [Table: see text]
Vascularized bone grafting fixed by biodegradable magnesium screw for treating osteonecrosis of the femoral head
Authors: Dewei Zhao, Shibo Huang, Faqiang Lu, Benjie Wang, Lei Yang, Ling Qin, Ke Yang, Yangde Li, Weirong Li, Wei Wang, Simiao Tian, Xiuzhi Zhang, Wenbin Gao, Zongpu Wang, Yu Zhang, Xinhui Xie, Jiali Wang, Junlei Li
Journal: Biomaterials (2015)
Splenectomy prolongs in vivo survival of erythrocytes differently in spectrin/ankyrin- and band 3–deficient hereditary spherocytosis
Authors: Ramune Reliene, Mariagabriella Mariani, Alberto Zanella, Walter H. Reinhart, M. Leticia Ribeiro, Emanuele Miraglia del Giudice, Silverio Perrotta, Achille Iolascon, Stefan Eber, Hans U. Lutz
Journal: Blood (2002)
A phase II study of HCVIDDOXIL alternated with methotrexate-cytarabine in patients with newly diagnosed T-cell lymphoma
Authors: B. Pro, L. Fayad, J. Romaguera, F. H. Hagemeister, F. Samaniego, P. McLaughlin, A. M. Rodriguez, L. Kwak, P. Walker, N. H. Dang
Journal: Journal of Clinical Oncology (2006)

7597 Background: T cell lymphomas (TCL) generally are more aggressive and have a poorer prognosis than the corresponding B cell lymphomas. A chemotherapeutic regimen that is effective in aggressive lymphoid malignancies is HCVAD alternating with methotrexate (MTX) and cytarabine (Ara-C). Pegylated liposomal doxorubicin (DOXIL) is associated with greater tumor penetration and less toxicity. We initiated a phase II study to evaluate the efficacy of the regimen HCVIDDOXIL, using DOXIL as a substitute for doxorubicin in the HCVAD regimen, alternated with MTX-Ara-C . Methods: Previously untreated patients (pts) with Zubrod performance status ≤3, age &gt; 18 years, and adequate organ function were eligible. Pts with skin involvement alone, CD30+, ALK +, T-anaplastic large cell lymphoma (ALCL), HIV-1 positive serology, and evidence of CNS involvement were excluded. Pts received HCVIDDOXIL ( cyclophosphamide 300 mg/m 2 iv Q 12 h × 6 doses d 1–3, mesna 600 mg/m 2 iv daily over 24 hours by continuous infusion d 1–3, DOXIL 25 mg/m 2 /day iv on d 2, vincristine 1.4 mg/m 2 (max. 2 mg) iv days 4 and 11, dexamethasone 40 mg iv or po daily × 4 d 1–4 and 11–14) alternated with MTX/Ara-C ( MTX 200 mg/m 2 iv over 2 hours on d 1, then 800 mg/m 2 iv over 22 hours on d1, Ara-C 3 g/m 2 iv Q 12 hours × 4 doses on d 3–4) every 3 weeks for a maximum of 8 cycles. Endpoints were progression-free survival and response rate. Results: Between October 2003 and November 2005, 23 pts were enrolled. Median age 53 years (range, 23–68). Twelve pts had stage IV, 6 stage III, 3 stage I, and 2 stage II disease. Fourteen (60%) pts had extranodal disease, and 8 (36%) pts had an elevated LDH. In 21 evaluable pts, the ORR was 90% [CR n=12 (57%); PR n= 7 pts (33%)]. Common Grade 3–4 adverse events were thrombocytopenia in 17 pts (77%), neutropenia in 6 (27%), anemia in 5 (23%), and febrile neutropenia in 7 (32%). With a median follow-up of 13 months, the median progression-free survival is 8.3 months (95% CI: 6.5 to 14.2 months). Conclusions: In this high-risk population the regimen HCVIDDOXIL alternated with MTX-Ara-C induced a high response rate. As expected, the most common toxicity was myelosuppression. The efficacy of this regimen should be confirmed in a larger cohort of patients. Enrollment in this study continues. No significant financial relationships to disclose.
Protein phosphatase 2A suppresses Bcl2’s antiapoptotic function by regulating Bcl2-p53 interaction
Authors: Xingming Deng, Fengqin Gao, Tammy Flagg, W. May
Journal: Cancer Research (2007)

1597   DNA damage-induced p53/Bcl2 interaction at the outer mitochondrial membranes results in a Bcl2 conformational change and loss of its antiapoptotic function. Protein phosphatase 2A (PP2A) is a physiological Bcl2 phosphatase which directly dephosphorylates Bcl2. Here we found that specific disruption of PP2A activity by the expression of SV40 small tumor antigen not only enhances Bcl2 phosphorylation but also suppresses the cisplatin-stimulated Bcl2-p53 interaction in association with prolonged cell survival. By contrast, C2-ceramide, a potent PP2A activator, reduces Bcl2 phosphorylation and increases Bcl2-p53 binding and promotes apoptotic cell death. Overexpression of the PP2A catalytic subunit (PP2A/C) suppresses Bcl2 phosphorylation in association with increased p53-Bcl2 binding and apoptotic cell death. By contrast, specific depletion of PP2A/C by RNA interference enhances Bcl2 phosphorylation, suppresses p53-Bcl2 interaction and prolongs cell survival. Purified PP2A can directly enhance the formation of the p53-Bcl2 complex in vitro in an okadaic acid-sensitive manner, suggesting that PP2A-induced dephosphorylation of Bcl2 promotes its interaction with p53. Importantly, PP2A directly interacts with Bcl2 at its BH4 domain which may function as the PP2A “docking site” to potentially “bridge” PP2A to the flexible loop domain which contains the physiological serine 70 phosphorylation site. Thus, PP2A may provide a double whammy to Bcl2’s survival function by both dephosphorylating and enhancing p53-Bcl2 binding. Therapeutically stimulating Bcl2 dephosphorylation and/or increasing Bcl2/p53 binding by activating PP2A may represent an efficient and novel antineoplastic approach.
Selective costimulation by IL-15R/IL-15, but not IL-2R/IL-2, allows the induction of high numbers of tumor-specific CD8+ T cells by human dendritic cells matured in conditions of acute inflammation
Authors: Morten Hansen, Eva Wieckowski, Inge Marie Svane, Robert P Edwards, Pawel Kalinski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Conventional dendritic cells (DC) are believed to rely on membrane-bound IL-2Rα to trans-present soluble IL-2 and costimulate T cell activation and expansion. In contrast, Langerhans cells have been shown to use membrane-bound IL-15Rα/IL-15 complex to activate T cells. Here we
Recruitment experience in a phase 0 trial of ABT-888, an inhibitor of poly (ADP-ribose) polymerase (PARP), in patients (pts) with advanced malignancies
Authors: M. Gutierrez, S. Kummar, Y. Horneffer, L. Juwara, A. Chen, G. Melillo, O. Pickeral, J. E. Tomaszewski, A. J. Murgo, J. H. Doroshow
Journal: Journal of Clinical Oncology (2007)

14111 Background: Phase 0 trials conducted under the FDA Exploratory IND Guidance involve limited exposures to study drug with no expectation of clinical benefit. We present our experience in recruiting pts to a Phase 0 study of ABT-888, the first to be conducted at the NCI. Methods: Objective: To determine the ABT-888 dose that inhibits PARP in PBMCs and tumor after a single oral administration. Tumor biopsies at baseline and 3–6 hrs post drug were planned once PARP activity inhibition in PBMCs or target plasma Cmax was achieved. Protocol was approved by the NCI scientific committee, IRB, and CTEP, and was reviewed by the NIH Ethics Committee. Informed consent included an explicit statement acknowledging the non-therapeutic, non-personal benefit nature of the study. Results: Since 6/06, 17 pts screened; 6 enrolled. Reasons for declining participation: Non-therapeutic study (2); biopsy requirement (2); recommendation by oncologist (2) or family member (2); condition requiring treatment (3). Reasons for participation: Altruism (4); altruism + waiting for another study (2). Of 6 pts enrolled, colon cancer (2), lymphoma (2), carcinoid (1), lung cancer (1). Median age: Participants (P) 57 (49–64) and non-participants (NP): 62 (42–78). Median prior therapies: P 3.6 (0–8) and NP: 3 (0–7). Referral origin for P: Prior participation on NCI studies (2), prior pt-NCI physician relationship (4). Ethnicity of P: White (5) and Hispanic (1). 3 of 6 pts underwent serial biopsies as required by protocol. Conclusion: Phase 0 recruitment is feasible and the accrual can be completed in a timely fashion, but depends on pt altruism and prior physician-pt relationship. These studies can be ethically conducted provided that interventions are of minimal risk, the study experience is commensurate with pt expectations, and that results are invaluable to subsequent pts. No significant financial relationships to disclose.
Multicenter phase II trial of interleukin-2, interferon-alpha, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma.
Authors: W M Stadler, T Kuzel, M Dumas, N J Vogelzang
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the response rate and toxicity of oral 13-cis-retinoic acid (CRA) added to an outpatient regimen of subcutaneous interleukin-2 (IL2) and interferon-alpha (IFNA) in previously untreated patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS Eligibility included a performance status of 2 or better, no significant end-organ dysfunction, and written informed consent. Characteristics of 47 of 48 assessable patients included a median performance status of 0, prior nephrectomy in 68% of patients, one metastatic site in 30% of patients, and lung-only metastatic disease in 21% of patients. Therapy consisted of IL2 11 x 10(6) IU 4 days per week for 4 weeks, IFNA 9 x 10(6) IU 2 days per week for 4 weeks, and CRA 1 mg/kg daily on a 6-week cycle. RESULTS Eight of 47 patients (17%) responded (one complete response, seven partial responses). Three partial responders were rendered disease free by subsequent surgical resection. Four additional patients experienced a minor response in lung or soft tissue metastases. The median duration of response, which included minor responses, was 42 weeks, and median survival was 74 weeks (17 months). Grades 3 or greater toxicities during the first cycle included flu-like symptoms (21% of patients), fatigue (6% of patients), and nausea and vomiting (15% of patients). Significant cumulative toxicities were hyperlipidemia (four of 18 patients), and cardiomyopathy (one of 18 patients). There was one therapy-related death. CONCLUSION Outpatient CRA plus IL2 and IFNA is feasible and modestly effective in metastatic RCC. The prolonged median survival is encouraging, but randomized trials are required to show that the combination represents an improvement over single-agent immunotherapy.
The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) Classification System
Authors: Erica S. Spatz, Leslie A. Curry, Frederick A. Masoudi, Shengfan Zhou, Kelly M. Strait, Cary P. Gross, Jeptha P. Curtis, Alexandra J. Lansky, Jose Augusto Soares Barreto-Filho, Julianna F. Lampropulos, Hector Bueno, Sarwat I. Chaudhry, Gail D’Onofrio, Basmah Safdar, Rachel P. Dreyer, Karthik Murugiah, John A. Spertus, Harlan M. Krumholz
Journal: Circulation (2015)

Background— Current classification schemes for acute myocardial infarction (AMI) may not accommodate the breadth of clinical phenotypes in young women. Methods and Results— We developed a novel taxonomy among young adults (≤55 years) with AMI enrolled in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study. We first classified a subset of patients (n=600) according to the Third Universal Definition of MI using a structured abstraction tool. There was heterogeneity within type 2 AMI, and 54 patients (9%; including 51 of 412 women) were unclassified. Using an inductive approach, we iteratively grouped patients with shared clinical characteristics, with the aims of developing a more inclusive taxonomy that could distinguish unique clinical phenotypes. The final VIRGO taxonomy classified 2802 study participants as follows: class 1, plaque-mediated culprit lesion (82.5% of women; 94.9% of men); class 2, obstructive coronary artery disease with supply-demand mismatch (2a: 1.4% women; 0.9% men) and without supply-demand mismatch (2b: 2.4% women; 1.1% men); class 3, nonobstructive coronary artery disease with supply-demand mismatch (3a: 4.3% women; 0.8% men) and without supply-demand mismatch (3b: 7.0% women; 1.9% men); class 4, other identifiable mechanism (spontaneous dissection, vasospasm, embolism; 1.5% women, 0.2% men); and class 5, undetermined classification (0.8% women, 0.2% men). Conclusions— Approximately 1 in 8 young women with AMI is unclassified by the Universal Definition of MI. We propose a more inclusive taxonomy that could serve as a framework for understanding biological disease mechanisms, therapeutic efficacy, and prognosis in this population.
Regulation of Snai2 by estrogen receptor-alpha and glycogen synthase kinase-3 beta in human breast cancer
Authors: Yin Ye, Sanford Barsky
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4402 

Snai2 (Slug), a member of the Snail family of C2H2-type zinc finger transcription factors, represses E-cadherin, a process which mediates in part epithelial-mesenchymal transition (EMT) in human breast cancer. Whereas much is known about the functions of Snai2, little is known about the regulation of this gene. In this study we report that both estrogen receptor alpha (ERα) and glycogen synthase kinase-3beta (GSK-3β) are key activators/regulators of snai2. ERα generally is thought to regulate gene expression by two mechanisms: direct activation/repression or proteolytic degradation of its target gene products through ubiquination pathways. Here, we report that snai2 is a target of ERα by both mechanisms. Our data show that treatment of ERα positive MCF-7 cells with 17-β estradiol (E2) decreases the level of snai2 mRNA and treatment of ERα-positive or negative cells with HDAC inhibitors leads to upregulation of snai2 expression. The snai2 mRNA increases when ERα is knocked down by shRNA in MCF-7 cells. Using the CHIP assay, ERα proteins bind to the upstream region of Snai2 promoter. Furthermore, in MCF-7 cells, N-CoR and SMRT bind to the same region of the snai2 promoter and ERα, N-CoR, SMRT, HDAC1 form a corepressor complex that suppresses the transcription of the snai2 gene. However, in the transgenic MDA-MB-468 cell line which expresses a full-size ERα, the levels of both snai2 mRNA and protein are found to increase, suggesting that ERα regulates snai2 transcription differently in a natively ERα negative line. Our data also show that ERα can bind with snai2 and promote the degradation of snai2 protein by ubiquination. With respect to GSK-3β, this kinase is a key activator of snai2. Using both the ERα negative MDA-MB-468 and -231 cell lines, we observed that the expression of snai2 is downregulated when the cell lines are treated with GSK-3 inhibitors and snai2 expression completely abolished when treated with LiCl, a specific GSK-3β inhibitor, indicating that it is GSK-3β and not GSK-3α, that regulates the expression of snai2. Snai2 expression also decreases when the cell lines are treated with IGF-I, which regulates the MAPK and the PI3K pathways. In contrast, the PI3K inhibitor, wortmannin, and the MAPK inhibitor, PD98059, increase snai2 expression suggesting that the release of suppression of GSK-3β correlates with the upregulation of snai2. We also found TGFβ decreases snai2 expression by suppressing GSK-3β through the MEK/ERK pathway. The same results were obtained from Wnt/frizzled/DSH pathway activation which leads to inhibition of GSK-3β with resulting inhibition of snai2 expression. GSK-3β plays a central and key role in activation of snai2. Predictably extracellular growth factors, such as TGFβ and IGF-I, also decrease snai2 expression through their regulation of GSK-3β. Both ERα and GSK-3β regulate snai2. These findings then link these genes to E-cadherin expression and EMT in human breast cancer.
Kidney iron status in passive Heymann nephritis and the effect of an iron-deficient diet.
Authors: R Baliga, N Ueda, S V Shah
Journal: Journal of the American Society of Nephrology (1996)

In the study presented here, the iron status in the kidney in passive Heymann nephritis, a complement-dependent model of membranous nephropathy, was examined. To examine whether the effect of immune injury on iron status has a pathogenic role, the effect of an iron-deficient diet was also determined. Injection of the anti-Fx1A antibody (10 mg/100 g body wt) in Sprague-Dawley rats resulted in no change in the serum iron level, a marked increase in the urinary excretion rate of iron, a marked increase in non-heme iron content of kidney cortex, and a marked increase in the non-heme iron level in tubules. These increases in iron were prevented by feeding the rats an iron-deficient diet. In the rats fed a normal iron diet and injected with anti-Fx1A-lgG, there was no significant change in the non-heme iron level in glomeruli. However, an iron-deficient diet resulted in a significant decrease in the non-heme iron level in glomeruli, compared with its respective control. In addition, an iron-deficient diet significantly reduced urinary protein excretion rate (Day 5: iron-replete, 68 +/- 12 mg/24 h, N = 12; iron-deficient, 36 +/- 11, N = 10, P < 0.05) in the complement-dependent immune phase of the glomerular injury. Taken together, these data indicate a marked alteration in the iron status in the kidney and suggest an important role of iron in glomerular injury of passive Heymann nephritis.
5-fluorouracil, adriamycin, and mitomycin in the treatment of adenocarcinoma of unknown primary.
Authors: R M Goldberg, F P Smith, W Ueno, J D Ahlgren, P S Schein
Journal: Journal of Clinical Oncology (1986)

The combination of 5-fluorouracil (5-FU), doxorubicin, and mitomycin (FAM) is often recommended for empiric management of patients with adenocarcinoma of unknown primary. This recommendation is based on the activity of FAM for adenocarcinomas of specific known sites of origin. A literature search disclosed no reports of the efficacy of FAM in this clinical entity. We report on 45 patients with biopsy-proven adenocarcinoma in whom investigation revealed no primary site and who were treated in a phase II trial with FAM. Of 43 evaluable patients, four achieved a complete tumor response, and nine obtained a partial response for an overall response rate of 30%. The median survival for all patients was greater than 10 months. The median survival for patients whose tumors were unresponsive to FAM was 6 months, and median survival was greater than or equal to 14 months in patients with stable disease or FAM-responsive tumors. A phase III trial comparing no therapy or 5-FU with FAM is warranted. For patients not treated in an investigative setting, FAM compares favorably with reported series using other regimens.
Adjuvant Radiation Therapy of Rectal Cancer
Authors: Joel E. Tepper
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.17.3709 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11533091 Adjuvant Radiation Therapy of Rectal Cancer Joel E. TepperxJoel E. TepperSearch for articles by this author Show More University of North Carolina School of Medicine, Chapel Hill, NC https://doi.org/10.1200/JCO.2001.19.17.3709 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology