tbuckley/cabot-search huggingface dataset:
Comparison of cytopathological and histological results in 1,053 fine-needle aspiration cytology of breast lesions performed in a one-stop clinic
Authors: I. Borget, C. Caramella, C. Balleyguier, V. Suciu, C. Uzan, J. Domont, M. Mathieu, C. Dromain, S. Delaloge, P. Vielh
Journal: Journal of Clinical Oncology (2009)

635 Background: Fine-needle aspiration cytology (FNAC) has been used extensively in the diagnosis of breast lesions, but false-negative rates are a matter of concern. However, immediate onsite evaluation of breast lesions, combining FNAC results with clinical and radiological data allows to improve its diagnostic accuracy. The objective of this study was to evaluate the concordance between cytopathological and histological results in a large series of FNAC performed during the first 3-yr period of the dedicated one-stop clinic set up in our institution since 2004. Methods: We reviewed data of all patients (pts) seen in the one stop clinic between May 2004 and March 2007 who had a lesion diagnosed by FNAC and verified by histology. For benign lesions, histological verification of the lesion was mandatory each time there was no perfect concordance between clinico-radiologic features and FNAC results (such as benign FNAC but BI-RAD 5). Pts characteristics, radiological findings, cytopathological and histological (by per-cutaneous biopsy or surgery) results were extracted from the hospital computerized prospectively registered medical records. Results: A total of 1053 nodular breast lesions (mean size: 24±23 mm, BI-RAD ACR 1/2/3/4/5: 2/10/68/283/684) in 1015 pts (mean age: 59±13 years) were studied. FNAC was US-guided in 521 lesions (49.4%). FNAC classified lesions as malignant in 741 (70.4%), benign in 127 (12.0%), suspicious in 143 (13.6%), and unsatisfactory in 42 (4.0%) cases. Among definitive benign or malignant diagnosis, FNAC and histological results showed concordance in 840/868 (96.7%) cases (738 malignant and 102 benign cases). The numbers of false-negative and false-positive lesions were respectively 25/127 (19%) and 3/741 (0.4%). Among the 143 suspicious and 42 unsatisfactory specimens, 114 and 20 were malignant, respectively. Conclusions: FNAC performed in a one-stop clinic allows obtaining an immediate on-site diagnosis of breast cancer with a good concordance with histological results and low rate of unsatisfactory specimens. However, affirming benign lesion requires a multi-disciplinary team: whenever clinico-radiologic features and FNAC results are non concordant, histologic assessment is mandatory. No significant financial relationships to disclose.
The effect and mechanism of M402 on gemcitabine uptake into pancreatic tumors.
Authors: Birgit Corinna Schultes, Chia Lin Chu, Alison Long, Elaine Sun, Elma Kurtagic, Daniela Beccati, Joel Pradines, Paul Miller, David P. Ryan, Keith Flaherty, James Roach, Ganesh Venkataraman Kaundinya
Journal: Journal of Clinical Oncology (2014)

215 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which has been attributed to high interstitial pressure and poor drug delivery. In nonclinical studies, M402 affected multiple growth factors, adhesion molecules, and chemokines, inhibiting tumor progression, metastasis, and angiogenesis by clearing heparin-binding factors from the tumor microenvironment. We hypothesized that M402 could modulate tumor-stroma interactions in an orthotopic pancreatic cancer model (rich in desmoplasia), decreasing the fibrotic response and in turn increasing tumor perfusion and drug delivery. Methods: Capan-2 human PDAC cells were injected into the pancreata of nude mice. M402 (40 mg/kg/day, s.c.) or saline began Week 5. Gemcitabine (GEM; 30 mg/kg, i.p. biweekly) started Week 7. At different time points, primary tumors were analyzed for mRNA arrays, immunohistochemistry (ECM components, CD31), and functional tumor vasculature. GEM tumor uptake was evaluated by quantifying the incorporation of dFdC into tumor DNA by LC-MS/MS. M402 tumor uptake was visualized using HyLite-750-labeled drug in a Xenogen system. Results: M402 readily targeted pancreatic tumors with long residence time. Alone and particularly in combination with GEM, M402 significantly reduced tumor size and fibrosis, which was accompanied by down-regulation of SHH, PDGF, and TGF-β signaling in stromal cells. Tumors treated with M402 or M402+GEM showed perfusion and microvessel penetration into the tumor centers while vehicle or GEM treated tumors exhibited limited tortuous vessels surrounding the tumor rim. This translated into increased GEM incorporation into the tumor DNA when mice were pre-treated with M402 vs. saline (10.9±5.5 vs. 6.7±1.8 pg of dFdC/µg dG, respectively; p=0.037). Conclusions: M402 appears to inhibit stromal activation within the tumor microenvironment. Reduction in desmoplasia led to improved tumor perfusion, delivery of GEM, and tumor shrinkage. These and other promising nonclinical data support the rationale for the ongoing Phase 1/2 study evaluating the safety and tolerability of M402 in combination with nab-paclitaxel and GEM in patients with metastatic pancreatic cancer.
Abstract 3107: MicroRNA-1289 is a novel tumor suppressive microRNA in human oral squamous cell carcinoma
Authors: Kazuki Iwamoto, Koh-ichi Nakashiro, Hiroshi Tnaka, Norihiko Tokuzen, Hiroyuki Hamakawa
Journal: Cancer Research (2015)

Abstract MicroRNAs (miRNAs) are small non-coding double-stranded RNA with sizes of approximately 22 nucleotides, and those inhibit protein translation by binding the 3′-untranslated region of target mRNAs. Each miRNA generally can regulate multiple mRNAs and each mRNA can be inhibited by a number of miRNAs. MiRNAs can behave as not only oncogenes but also tumor suppressive (TS) genes in human malignancies. In fact, a number of TS miRNAs (TS-miRs) were found in human many types of cancer, such as let-7, miR-1, miR-34, miR-145, miR-200, miR-206 and more. In this study, we have attempted to identify a novel TS-miR in human oral squamous cell carcinoma (OSCC) using function-based screening. First, we transfected human OSCC cells (GFP-SAS) with approximately 1,000 synthetic mimicking human mature miRNAs at the concentration of 20 nM complexed with Lipofectamine RNAiMAX. After transfection for 72 hours, the growth of these cells was evaluated by WST-8 assay. As a result, miR-1289 had the most potent growth inhibitory effect against GFP-SAS cells. The growth rate of these cells transfected with miR-1289 was reduced by 86.4%. MiR-1289 also remarkably inhibited the growth of other human OSCC cells (Ca9-22, HSC2, HSC3 and primary cultured cells). Subsequently, we assessed the growth inhibitory effect of miR-1289 in vivo using a mouse model. GFP-SAS cells (2 × 106) complexed with matrigel in 100 μl aliquots were injected subcutaneously in nude mice. After tumor formation, we administered 100 ng of miRNA with 0.5% atelocollagen complexes (100 μl) around tumor every 3 days for a total of 5 injections. MiR-1289/atelocollagen complex administration group significantly reduced the size of subcutaneously xenografted GFP-SAS tumors compared with the control group. Next, we investigated the expression of miR-1289 in OSCC tissues by real-time quantitative RT-PCR. The expression levels of miR-1289 were significant decreased in OSCC tissues compared to adjacent normal oral mucosa tissues. Finally, target genes of miR-1289 were explored by microarray and Ingenuity Pathway Analysis (IPA). Microarray analysis revealed that the expression levels of 51 genes were commonly down-regulated in OSCC cells (GFP-SAS, Ca9-22 and HSC2) by transfection with miR-1289. Among these genes, 15 genes were identified as target genes of miR-1289 by IPA. These results suggest that miR-1289 functions as a novel TS-miR in OSCC, and may be a useful therapeutic tool for the patients with OSCC. Citation Format: Kazuki Iwamoto, Koh-ichi Nakashiro, Hiroshi Tnaka, Norihiko Tokuzen, Hiroyuki Hamakawa. MicroRNA-1289 is a novel tumor suppressive microRNA in human oral squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3107. doi:10.1158/1538-7445.AM2015-3107
Role of the ABC-transporters ABCC4, ABCC5 and ABCC11 in response to chemotherapy in adult patients with acute myeloid leukemia
Authors: Christoph A. Ritter, Kathleen Köck, Gabriele Jedlitschky, James F. Beck, Gerhard Ehninger, Heyo K. Kroemer, Markus Schaich
Journal: Cancer Research (2005)

6169   Resistance to chemotherapeutic drugs is a major factor limiting a successful therapy. One proposed mechanism for treatment failure in patients with acute myeloid leukemia (AML) is the efflux of cytostatics. The multidrug resistance-associated proteins ABCC4, ABCC5 and ABCC11 have the ability to transport cyclic nucleotides and anti-cancer nucleoside analogs. These substances are particularly valuable for the treatment of AML, which is the most common form of leukemia in adults. Therefore we examined the clinical relevance of ABCC4, ABCC5 and ABCC11 by analyzing their mRNA expression levels in pre-treatment leukemic blast cells of the bone marrow of 50 newly diagnosed AML-patients participating in the SHG-AML-96 study. mRNA expression levels were investigated by quantitative TaqMan Real-time PCR and normalized to 18S mRNA expression. The median relative mRNA expression levels of the patient probes were different between the three examined genes (28.8 (ABCC4), 63.7 (ABCC5), 0.34 (ABCC11)). There was no significant association with age, white blood cell count, frequency of blast cells in bone marrow and P-gp mRNA level, but patients with the French-American-British (FAB) subtype M1 showed a higher mRNA expression of all genes examined (P ABCC4 =0.002; P ABCC5 =0.007; P ABCC11 =0.004). For ABCC4 and ABCC5 no significant association was found for complete remission rate and overall survival. However, Kaplan-Meyer statistics and Log-rank test suggest that despite its low mRNA expression ABCC11 has a negative influence on overall survival with a 5 year probability of survival of 28% for patients with low and only 8% for patients with high ABCC11 expression (P=0.03). As complete remission rate was not affected this was mainly due to a higher relapse rate in high ABCC11 expressing patients. In conclusion, ABCC11 expression seems to be a new promising predictor for treatment outcome in adult AML.
Psychoanalytic-Interactional Therapy versus Psychodynamic Therapy by Experts for Personality Disorders: A Randomized Controlled Efficacy-Effectiveness Study in Cluster B Personality Disorders
Authors: Falk Leichsenring, Oliver Masuhr, Ulrich Jaeger, Sven Rabung, Andreas Dally, Michael Dümpelmann, Christian Fricke-Neef, Christiane Steinert, Ulrich Streeck
Journal: Psychotherapy and Psychosomatics (2016)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; With regard to cluster B personality disorders, most psychotherapeutic treatments focus on borderline personality disorder. Evidence-based treatments for patients with other cluster B personality disorders are not yet available. Psychoanalytic-interactional therapy (PIT) represents a transdiagnostic treatment for severe personality disorders. PIT has been applied in clinical practice for many years and has proven effective in open studies. In a randomized controlled trial, we compared manual-guided PIT to nonmanualized pychodynamic therapy by experts in personality disorders (E-PDT) in patients with cluster B personality disorders. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In an inpatient setting, patients with cluster B personality disorders were randomly assigned to manual-guided PIT (n = 64) or nonmanualized E-PDT (n = 58). In addition, a quasi-experimental control condition was used (n = 46) including both patients receiving treatment as usual and patients waiting for treatment. Primary outcomes were level of personality organization and overall psychological distress. As secondary outcomes, depression, anxiety and interpersonal problems were examined. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; No significant improvements were found in the control patients. Both PIT and E-PDT achieved significant improvements in all outcome measures and were superior to the control condition. No differences were found between PIT and E-PDT in any outcome measure at the end of treatment. The type of cluster B personality disorder had no impact on the results. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In an inpatient setting, both PIT and E-PDT proved to be superior to a control condition in cluster B personality disorders. In a head-to-head comparison, both treatments appeared to be equally effective. Further research on the treatment of cluster B personality disorders is required.
Ecto-5′-Nucleotidase. II. Effect of 12-&lt;italic&gt;O&lt;/italic&gt;-Tetradecanoylphorbol 13-Acetate on the Expression of Enzyme in Normal and Neoplastic B-Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: T Hibi, S SenGupta, A MacKay, E W Gelfand, B E Chechik
Journal: JNCI Journal of the National Cancer Institute (1984)

Immature B-cells, including B-cell lymphoma lines, are often deficient in ecto-5'-nucleotidase (5'-NT) activity. 12-O-Tetradecanoylphorbol 13-acetate (TPA) was shown to be capable of inducing maturation toward plasmacytoid-like cells in immunoglobulin (Ig)-secreting B-cell lines. An attempt was made to induce the enzyme in 5'-NT-negative B-cell lymphoma lines with TPA to clarify the relationship between 5'-NT and B-cell differentiation. After 3 days in the presence or absence of TPA, these cell lines were examined morphologically, and their 5'-NT activity, Ig secretion, surface Ig, and Ia, B1, and B2 antigens were estimated. Neither Ig secretion nor 5'-NT activity was induced by TPA in any of 4 nonsecreting cell lines studied. Ig secretion was significantly increased in 4 of 5 lg-secreting cell lines. Two of these inducible cell lines, JD 38 and ST 486, became positive for 5'-NT activity and acquired morphologic characteristics of plasma cells after culture with TPA. The lymphoma cell line JD 38 was transplanted into nude mice and gave rise to a solid tumor. Although the tumor cells remained negative for 5'-NT, they could be induced by TPA to express both the enzyme activity and plasmacytoid-like appearance. These data suggested that in the Ig-secreting B-cell lymphoma lines, there was an association between the inducibility of 5'-NT and the capacity of these cell lines to undergo plasma-cytoid-like transformation in response to TPA.
Risk factors and treatment outcomes of spinal recurrence from intracranial germinoma
Authors: K. Ogawa, Y. Yoshii, N. Shikama, K. Nakamura, T. Uno, H. Onishi, J. Itami, Y. Shioyama, H. Ito, S. Murayama
Journal: Journal of Clinical Oncology (2008)

2086 Background: To analyze retrospectively the risk factors of spinal recurrence in patients with intracranial germinoma and clinical outcomes of patients who developed spinal recurrence. Methods: From 1980 to 2007, 165 patients with no evidence of spinal metastases at diagnosis were treated with cranial radiotherapy without spinal irradiation. One hundred three patients (62%) were treated using a radiation field encompassing the whole brain with or without a boost, 43 patients with the whole ventricle with or without a boost, and 19 patients with a localized-field smaller than the whole ventricle. The total dose to the primary site ranged from 24 to 59.5 Gy (median: 48.5 Gy). Seventy-five patients (45%) received systemic chemotherapy during the initial treatment and the median follow-up in all 165 patients was 61.2 months (range, 1.2–260.1 months). Results: After the initial treatment, 15 patients (9.1%) developed spinal recurrences. Multivariate analysis revealed that intracranial large (> 4 cm) disease and intracranial multiple/disseminated disease were independent risk factors for spinal recurrence. Radiation field, total radiation dose and the use of chemotherapy did not affect the occurrence of spinal recurrence. Concerning 15 patients who experienced spinal recurrence, the 3-year actuarial overall survival and disease-free survival (DFS) rates from the beginning of salvage treatments were 65% and 57%, respectively. In the analysis, presence of intracranial recurrence and salvage treatment modality (radiotherapy with chemotherapy vs. radiotherapy alone) had a statistically significant impact on DFS. The 3-year DFS rate in patients with no intracranial recurrence and treated with both spinal radiotherapy and chemotherapy was 100%, while only 17% in patients with intracranial recurrence and/or treated with radiotherapy alone (p = 0.001). Conclusions: When treating patients with intracranial germionma with no evidence of spinal metastases at diagnosis, craniospinal irradiation appears to be appropriate for patients with intracranial large disease and intracranial multiple/disseminated disease. For patients with spinal recurrence alone, salvage treatment combined with spinal radiotherapy and chemotherapy could control the recurrent disease. No significant financial relationships to disclose.
Phase I study of combination drug purging for autologous bone marrow transplantation.
Authors: S D Rowley, C B Miller, S Piantadosi, J M Davis, G W Santos, R J Jones
Journal: Journal of Clinical Oncology (1991)

In a phase I clinical trial of autologous bone marrow transplantation, we determined the feasibility of ex vivo purging with high concentrations of pharmacologics in combination. Light-density cells isolated from the grafts of 26 patients with acute leukemia or lymphoblastic lymphoma were treated with 4-hydroperoxycyclophosphamide (4-HC; 30 to 60 micrograms/mL), vincristine (Vcr; 1.5 to 3.0 micrograms/mL), and methylprednisolone sodium succinate (MP; 5 mg/mL). All patients received marrow-lethal induction therapy followed by infusion of the treated grafts. Three patients died of transplant-related complications before achieving peripheral blood recovery of greater than 0.5 x 10(9) granulocytes per liter. All other patients achieved this parameter of engraftment at a median of 35 days after marrow infusion. The median time to last platelet transfusion was 45 days. These durations of aplasia were similar to those experienced by other patients receiving density-gradient separated grafts treated with 60 micrograms/mL of 4-HC as a single agent. No patient required infusion of untreated reserve marrow because of engraftment failure. The colony-forming unit-granulocyte macrophage (CFU-GM) content of the grafts after purging predicted these parameters of engraftment. Colony-forming unit-leukemia (CFU-L) cultured from the grafts of 12 of the patients treated for acute lymphoblastic leukemia (ALL) were considerably more sensitive to the combination regimen than to 4-HC alone; the sensitivity of CFU-GM from these patients did not differ between the two regimens. The results of this trial indicate the feasibility of treating autologous bone marrow grafts with high concentrations of pharmacologics in combination. The use of combinations may increase the efficacy of ex vivo purging without increasing the toxicity to normal hematopoietic cells.
Epithelial-mesenchymal transition (EMT) in resected pancreatic cancer
Authors: V. D. Yosuico, T. Khoury, J. Yu, A. Pande, M. Javle
Journal: Journal of Clinical Oncology (2006)

4094 Background: EMT plays an important role in tumor invasion and metastases; its detection may have prognostic significance. We examined expression of EMT related proteins in resected pancreatic cancers and correlated results with clinical outcome. Methods: Clinical data/surgical specimens from 34 consecutive pancreatic cancer patients (pts) who underwent pancreatectomy from 1996–2002 were included. Immunohistochemical staining for vimentin (Vim 3B4), E-cadherin (36B5), MIB1 and cytokeratin (CK-AE1/AE3) was performed on formalin fixed paraffin embedded tissues. Percentages of stained cells (cytoplasmic for vimentin and CK, nuclear for MIB1 and membranous for E-cadherin) were recorded. The results were correlated with clinicopathological parameters and survival. Survival analysis (log-rank test, Cox-proportional hazard model), categorical data analysis (Pearson’s chi-square, logistic regression) and Kendall’s tau were performed at the significance level of 0.05. Results: Clinical data/specimens from 34 pts were included: 13 males, median age 66 (range 38–84); SEER stage 1 (2 pts), 2 (27 pts), 3 (5 pts); histological grade 1 (4), 2 (13), 3 (16), 4 (1). Median survival was 15 months (95% CI: 11–24 months). Sixteen pts had adjuvant chemoradiotherapy, 4 pts had chemotherapy, 1 pt had radiation. IHC Results: vimentin (11.8%), MIB1 (100%), E-cadherin (91%) and CK (100%). There was a significant negative association between vimentin and E-cadherin expression (Kendall’s tau = −0.47, p = 0.0024). Vimentin expression correlated with histological grade (exact chi-square p = 0.0247). No associations were found between these proteins and SEER stage, age, treatment or smoking. Univariate analysis revealed histological grade 50% (p = 0.0039) and MIB1 expression &gt;10% (p = 0.0224) were related to better survival. Multivariate analysis using Cox-proportional hazard model revealed the following significant variables: histological grade (hazard ratio (HR) = 11.8, p = 0.0001), age (HR = 1.1, p = 0.0053), MIB1 (HR = 0.9, p = 0.0003) and adjuvant chemotherapy (HR = 0.2, p = 0.0288). Conclusion: Decreased E-cadherin expression (&lt;50% expression) was associated with poorer survival; E-cadherin expression had an inverse correlation with vimentin. Acknowledgement: Supported by OSI Pharmaceuticals. [Table: see text]
Survival Experience of Cancer Patients Enumerated in Morbidity Surveys
Authors: William Haenszel, Leonard Chiazze
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Survival Experience of Cancer Patients Enumerated in Morbidity Surveys Get access William Haenszel, William Haenszel Biometry Branch, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Leonard Chiazze, Jr. Leonard Chiazze, Jr. Biometry Branch, National Cancer Institute,3Bethesda, Maryland 2We wish to acknowledge the assistance of Herman Heise, William Lourie, and Samuel C. Marcus, who were responsible for direction and completion of field work in Chicago, Dallas, and Pittsburgh. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 34, Issue 1, January 1965, Pages 85–101, https://doi.org/10.1093/jnci/34.1.85 Published: 01 January 1965 Article history Received: 18 June 1964 Published: 01 January 1965