tbuckley/cabot-search huggingface dataset:
Long-term results of salvage cryotherapy for prostate cancer.
Authors: A. Williams, C. Martinez, V. Chalasani, C. Lu, C. Ng, S. E. Pautler, J. Chin
Journal: Journal of Clinical Oncology (2011)

108 Background: The optimum treatment of Prostate cancer recurrence following external bean radiation therapy (EBRT) remains a controversial topic. The primary problem with comparing salvage techniques following EBRT is the lack of long term data. We reviewed the long- term overall survival, disease-specific survival and disease free survival of patients who have undergone salvage cryotherapy to the prostate gland. Methods: A retrospective analysis was performed on all patients undergoing salvage cryotherapy for locally recurrent prostate cancer after EBRT by a single surgeon at a single institution from 1995-2004. Patients preoperative, perioperative and postoperative data was reviewed and recorded. Should a patient no longer be followed by the urology service the Patients and the patient's primary care physician or urologist were contacted. Mortality data, PSA results, bone scan results and any details of hormone therapy were recorded for this study. Results: 187 patients were included in the current study from which 176 patients had records available for follow up giving a follow up rate of 94%. Mean follow up was 7.46 years (1-14 years). 52 patients were followed for greater than 10 years. Average time to prostate cancer recurrence in patients who developed recurred was 2.3 years and average time to hormone therapy in these patients was 2.8 years. Overall survival at 10 years was high at 87%. Risk factors for recurrence of tumour identified were presalvage PSA, preradiation and presalvage gleason score. Preradiation gleason score had little impact on survival. PSA nadir of &gt;1.0ng/mL was highly predictive of early recurrence. Disease-free survival rates of between 39 and 64% depending on risk factors. Conclusions: Cryotherapy has a definite role in the management of prostate cancer, representing a minimally invasive salvage treatment with acceptable 10 year disease free survival (DFS) of upwards of 39% and specific groups attaining 10 year DFS of 64%. Presalvage PSA and Gleason score are the best predictors of disease recurrence, whilst preradiation gleason score did not correlate with risk of disease recurrence. A PSA Nadir greater than 1 ng/mL indicates a poor prognosis in which early ADT should be strongly considered. No significant financial relationships to disclose.
Use of a surgically derived nomogram to predict high likelihood of Gleason score upgrading for favorable-risk prostate cancer treated with permanent seed brachytherapy.
Authors: D. Bowes, J. M. Crook, K. Wallace, A. Evans, A. Toi, A. Finelli, M. A. Jewett
Journal: Journal of Clinical Oncology (2011)

114 Background: Crook et al have reported a 7-year disease-free survival (DFS) of 95.2% in 1,111 men with prostate cancer treated with Iodine-125 permanent seed brachytherapy (BT) at Princess Margaret Hospital. Two nomograms have been developed that estimate the likelihood of Gleason score (GS) upgrading for patients with favorable risk prostate cancer undergoing radical prostatectomy (RP). The purpose of this project was to apply these nomograms to a cohort treated with BT. Methods: Records were examined for all men receiving prostate BT in 2006-7. 217 had favorable risk disease. The likelihood of GS upgrading was predicted using RP-derived nomograms created by Kulkarni et al (PMH, 2007) and Budaus et al (2010). Clinical and pathologic information were available on 208 patients to allow completion of the Kulkarni nomogram, and on 193 patients for the Budaus nomogram. Results: The median age of the BT cohort was 62 years (range 44–77), and the median PSA level 4.68 ng/ml. Clinical stage was T1 in 65%, and 47.6% had positive findings on transrectal ultrasound. Median prostate volume was 33.3 cc (15.0–72.3). Uro-pathology review was available for 93%. 84.1% had extended biopsies, with 40.9% showing prostatic intraepithelial neoplasia and 10.1% inflammation. The median % of positive cores was 25%, with a median maximum % involvement per core of 20%. Two men received androgen deprivation therapy for prostate downsizing. The median predicted likelihood of GS upgrading was 51.6% using the Kulkarni nomogram, and 43.6% using the Budaus nomogram. The median PSA after 3.2 years median follow-up is 0.18 ng/mL. Conclusions: In a population of men with favorable risk prostate cancer treated with BT, the estimated likelihood of GS upgrading using two surgical nomograms was substantial. The study cohort was taken from a larger population of patients treated over 10 years for whom 7-year DFS is 95.2%. This suggests that permanent seed brachytherapy is a highly effective treatment option for patients with favorable risk disease despite unfavorable clinical and pathologic factors. Patients should not be discouraged from brachytherapy on the basis of a high likelihood of GS upgrading. No significant financial relationships to disclose.
Patient-Reported Outcomes from a Global Phase 3 Randomized Controlled Trial of Inotuzumab Ozogamicin Versus Standard of Care Chemotherapy for Relapsed/Refractory Acute Lymphoblastic Leukemia
Authors: Hagop M. Kantarjian, Yun Su, Elias J. Jabbour, Helen Bhattacharyya, Eric Yan, Mark Shapiro, Joseph C. Cappelleri, David I. Marks
Journal: Blood (2016)
Azacytidine (AZA) in MDS (including RAEB-t and CMML) in Patients (pts) ≥ 80 Years: Results of the French ATU Program.
Authors: Raphael Itzykson, Sylvain Thépot, Bechir Achour, Bruno Quesnel, Francois Dreyfus, Pascal Turlure, Anne-Laure Taksin, Norbert Vey, Anne Marfaing Koka, Stephane de Botton, Eric Wattel, Francoise Isnard, Isabelle Plantier, Caroline Dartigeas, Chahinez Zerhouni, Claude Gardin, Lionel Ades, Odile Beyne-Rauzy, Pierre Fenaux
Journal: Blood (2009)
Multi-institutional outcomes following LDR brachytherapy in patients with higher-risk prostate cancer.
Authors: Ruth Conroy, Peter Hoskin, David Bottomley, Paula Mandall, Ric Swindell, James Wylie
Journal: Journal of Clinical Oncology (2012)

238 Background: We report the outcomes for a cohort of men with higher risk prostate adenocarcinoma treated with LDR brachytherapy in a multi-institutional UK practice. Methods: 217 men treated between 2003-2007 with Iodine-125 brachytherapy at Christie, Leeds and Mount Vernon were identified from a multi-institutional database. Higher risk was defined as patients with ≥ 2 D’Amico intermediate risk factors (PSA 10-20, GS 7 or clinical T2c) or ≥1 high risk factor (PSA &gt; 20, GS ≥ 8). Kaplan-Meier methods were used to estimate biochemical relapse free survival (BRFS) defined using both Phoenix and ASTRO definitions. A univariate analysis was performed to assess the significance of Gleason score, PSA, T-stage, pre- or post-implant dosimetry, and additional hormones on BRFS. Results: The median age was 65yrs (43–79yrs) with a median PSA follow up of 62months (14–102months). Median pre-implant doses (ranges) were: V150 59.6(43.7–89.8), V200 20.1(11.6–36). 75 patients had post-implant dosimetry, median dose (range) was: D90 132.8Gy (75-192Gy). No patients had external beam radiotherapy. 67 patients had additional hormone treatment, median duration 7 months (3 – 22 months). The 3 and 5 year BRFS as defined by Phoenix were 85.4% and 74.4% and as defined by ASTRO were 76.6% and 69.8%. On univariate analysis there were no statistically significant predictors of inferior outcome. Conclusions: Single modality LDR brachytherapy is a well established treatment for low risk prostate adenocarcinoma reporting excellent long term BRFS. Some authors have advocated the addition of external beam radiotherapy when treating higher risk disease. These results show that good BRFS can be obtained with LDR brachytherapy alone and no additional benefit has been shown by the addition of adjuvant hormone therapy. These results appear comparable with other treatment modalities available to these patients.
Efficacy of a Dose-Intensified CHOP (Double-CHOP) Regimen for Peripheral T-Cell Lymphomas
Authors: Hiromichi Takahashi, Noriyoshi Iriyama, Yoshihiro Hatta, Katsuhiro Miura, Yujin Kobayashi, Daisuke Kurita, Yukio Hirabayashi, Atsuko Hojo, Hitomi Kodaira, Mai Yagi, Satomi Kiso, Yoshihito Uchino, Masaru Nakagawa, Machiko Kusuda, Sumiko Kobayashi, Akira Horikoshi, Yoshimasa Kura, Tetsuo Yamazaki, Umihiko Sawada, Jin Takeuchi
Journal: Blood (2012)
Identification of a small-molecule inhibitor of Stat5a/b through structure-based screen for therapy development for prostate cancer.
Authors: Z. Liao, L. Gu, F. Shen, A. Dagvadorj, S. Gupta, N. Pattabiraman, M. T. Nevalainen, E. J. Trabulsi, L. G. Gomella, P. McCue
Journal: Journal of Clinical Oncology (2011)

17 Background: There are no effective treatments for metastatic or castration resistant prostate cancer. We have shown that transcription factor Stat5a/b is constitutively active in high-grade prostate cancer, but not in normal human prostate epithelium. Stat5a/b is active in 95% of clinical castration resistant prostate cancers, and the expression of active Stat5a/b in primary prostate cancer predicts early disease recurrence. Stat5a/b is critical for the viability of prostate cancer cells in vitro and for growth of prostate xenograft tumors in nude mice. Stat5a/b synergizes with androgen receptor (AR) and Stat5a/b promotes metastatic behavior of human prostate cancer cells in vitro and in vivo. Here, we hypothesize that Stat5a/b is a molecular target for rational drug design for prostate cancer. Methods: We identified a small- molecule inhibitor of Stat5a/b dimerization by structure-based virtual screen from a database of 30 million chemical structures. The efficacy of the Stat5a/b inhibitor was determined by reporter gene assays, dimerization by co-immunoprecipitations, nuclear translocation by cytochemistry and binding to DNA by EMSA. Cell viability was analyzed by MTT assay. Results: The novel Stat5a/b inhibitor IST5-002 inhibited transcriptional activity of Stat5a/b at IC 50 of 1.5 μ M for Stat5a and 3.5 μ M for Stat5b, but not of Stat3 in prostate cancer cells. IST5-002 inhibited dimerization, nuclear translocation, and binding of Stat5a/b to the Stat5 DNA consensus sequence. Furthermore, IST5-002 inhibited expression of Stat5a/b target gene cyclin D1, and induced massive apoptosis of DU145, CWR22Rv1 and LNCaP human prostate cancer cells. IST5-002 blocked prostate cancer xenograft tumor growth in nude mice and induced death in clinical prostate cancers ex vivo in 3D organ cultures. Conclusions: We have identified a small molecule Stat5a/b inhibitor IST5-002 for therapy development for prostate cancer. Future work will focus on chemical modifications of IST5-002 to achieve IC 50 below 1 μ M and oral administration. No significant financial relationships to disclose.
RECQL4 Modulates MDR1 Expression and Chemoresistance—Letter
Authors: Paola Perego
Journal: Cancer Research (2016)

I read with interest the article about cisplatin resistance in gastric cancer by Mo and colleagues ([1][1]). Their study shows that the DNA unwinding helicase RECQL4, which is involved in the formation and maintenance of the replication fork ([2][2]), plays a prognostic role in such an aggressive
Circulating tumor cells (CTCs) as a predictor of metastatic disease in patients with biochemical recurrence (BR) of prostate cancer with equivocal scan results.
Authors: Jeanny B. Aragon-Ching, Samuel J. Simmens, Steven R. Patierno, Robert S. Siegel
Journal: Journal of Clinical Oncology (2012)

239 Background: Staging for BR is challenging since the yield of computed tomography (CT) and bone scans are low, especially in patients with low prostate specific antigens (PSA) levels. We examined the utility of circulating tumor cells (CTCs) to predict metastatic disease in a cohort of patients who presented with BR (Aragon-Ching, et. al. ASCO GU 2011;abstr 60). Methods: 33 pts enrolled from May 2010 to September 2011 with BR, defined as patients (pts) who have undergone primary treatment with PSA rise to &gt;/= 0.2 from a prior undetectable level for prior prostatectomy or &gt; 2 mg/dl rise from post-nadir radiotherapy, were included. PSA doubling time (PSADT), scan results, Gleason scores, age, testosterone levels were all obtained. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. BR patients with equivocal CT and/or bone scan results who were biopsiable and consentable underwent bone biopsy to confirm metastatic disease. Results: The median age for 33 patients was 71 y/o (range: 51 – 91), median PSA of 1.7 ng/mL (range 0.2 – 65.8), testosterone levels of 315.5 ng/dL (range: 31 – 727), Gleason score of 7, hemoglobin of 13.78 g/dL, BMI of 27.72 and alkaline phosphatase of 68 IU/L. Prostatectomy was the primary treatment in 23 pts, radiotherapy in 9 pts and Cyberknife in 1 pt. Median PSADT varied between 0.35 to 55.2 months. Only a small number of patients had either biopsy confirmed metastatic disease (n=2) or detectable CTC (n=3). Both of the 2 patients with metastatic disease had detectable CTC (sensitivity = 1.00, 95% CI: .34, 1.00). For the patients without signs or confirmation of metastatic disease, 30/31 had no detectable CTC (specificity = .97, 95% CI: .84, .99). Conclusions: While most pts with BR have negative blood CTCs, patients with detectable CTCs and equivocal findings on scans should raise suspicion and prompt a search for metastatic disease, given increasing available treatment options for metastatic prostate cancer. However, the limited number of patients may preclude reliable statistical evaluation of CTCs in this population. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.
High Incidence of Thrombotic Events Observed in Patients Receiving Lenalidomide (L) + Dexamethasone (D) (LD) as First-Line Therapy for Multiple Myeloma (MM) without Aspirin (ASA) Prophylaxis.
Authors: Jeffrey A. Zonder, Brian G.M. Durie, Jason McCoy, John Crowley, Jerome B. Zeldis, Lena Ghannam, Bart Barlogie
Journal: Blood (2005)
Explaining consciousness: From correlations to foundations
Authors: Wolfgang Prinz
Journal: Behavioral and Brain Sciences (2016)

Abstract What does it take to explain the roles of consciousness for action and action for consciousness? This commentary claims that efficient functional explanations must meet two epistemological requirements: independent description of explanandum and explanans, and foundational explanation of their mutual relationship. It is argued that Morsella et al.'s target articledoes not fully meet these requirements.
STAT3 signaling drives EZH2 transcriptional activation and mediates poor prognosis in gastric cancer
Authors: Yuan-Ming Pan, Cheng-Gang Wang, Min Zhu, Rui Xing, Jian-Tao Cui, Wen-Mei Li, De-Dong Yu, Shu-Bin Wang, Wei Zhu, Ying-Jiang Ye, Yun Wu, Shan Wang, You-Yong Lu
Journal: Molecular Cancer (2016)

STAT3 signaling plays the pivotal role in tumorigenesis through EZH2 epigenetic modification, which enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3. Here, another possible feedback mechanism and clinical significance of EZH2 and STAT3 were investigated in gastric cancer (GC). STAT3, p-STAT3 (Tyr 705) and EZH2 expression were examined in 63 GC specimens with matched normal tissues by IHC staining. EZH2 and STAT3 were also identified in five GC cell lines using RT-PCR and western blot analyses. p-STAT3 protein was detected by western blotting. In order to investigate whether EZH2 expression was directly regulated by STAT3, EZH2 expression was further detected using siRNA for STAT3 or IL-6 stimulation, with dual luciferase reporter analyses, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. The clinical significance of STAT3, p-STAT3 and EZH2 expression was evaluated by multi-factor COX regression and Kaplan-Meier analyses. Hyper-activation of STAT3, p-STAT3 and EZH2 expression were observed in GC cells and tissues. STAT3 signaling was correlated with EZH2 expression in GC (R = 0.373, P = 0.003), which was consistent with our data showing that STAT3 as the transcriptional factor enhanced EZH2 transcriptional activity by binding the relative promoter region (-214 ~ -206). STAT3 was an independent signature for poor survival (P = 0.002). Patients with STAT3+/EZH2+ or p-STAT3+/EZH2+ had a worse outcome than others (P < 0.001); Besides, high levels of STAT3 and EZH2 was associated with advanced TNM staging (P = 0.017). Moreover, treatment with a combination of siSTAT3 and EZH2-specific inhibitor, 3-deazaneplanocin A (DZNEP), increased the apoptotic ratio of cells. It is benefit for targeting STAT3-EZH2 interplay in GC treatment. Our results indicate that STAT3 status mediated EZH2 upregulation, associated with advanced TNM stage and poor prognosis, suggesting that combination with knockdown of STAT3 and EZH2 inhibitor might be a novel therapy in GC treatment. Collectively, STAT3, p-STAT3 and EZH2 expression were provided for the precision medicine in GC patients.
Neoadjuvant chemotherapy (NAC) consisting in dose-dense doxorubicin plus cyclophosphamide followed by cisplatin plus taxane for locoregional advanced triple-negative breast cancer (LATNBC).
Authors: E. Diaz-Correa, C. Singh, R. Pereira
Journal: Journal of Clinical Oncology (2011)

e11562 Background: Despite TNBC use to be a chemosensitive tumor, it carries a very bad prognosis and this is particularly true in local and regional advanced disease. Nevertheless when pathologic complete response (pCR) to NAC is achieved, the prognosis improves and changes to be good. About 75% of TNBC correspond to basal like carcinomas (BLC) that are associated to BRCA1 mutations and Cisplatin sensibility. Also is known that dose dense chemotherapy is superior that standard every 3 weeks chemotherapy when is administered as adjuvant treatment. Methods: Twenty one consecutive patients (pts) with LATNBC were included from December 2006 to December 2009. Median age was 45 years (33-68), 14 (66.6%) premenopausal. Two pts were excluded because of treatment violation. Nineteen were evaluable. The clinical stages were: 1 IIB (5%), 10 IIIA (53%), 6 IIIB (32%) and 2 IIIC (10%); 3 (16%) grade 2 and 16 (84%) grade 3 of Nottingham. Seventeen of 19 tumors (89.5%) were positive for CK 5/6 (14/19), EGFR (12/19) or both as markers of BLC subtype by immunohistochemistry. NAC consisted in 4 cycles of Doxorubicin 55 mg/m2 and Cyclophosphamide 550 mg/m2 every 2 weeks with G-CSF support 300 ug on days -3 and -2 before cycles 2, 3 and 4. Then the treatment was changed to either Paclitaxel 80 mg/m2 (12 pts) every week for 12 weeks or Docetaxel 100 mg/m2 (7 pts) every 3 weeks for 4 cycles. At the same time, Cisplatin was started at 75 mg/m2 every 3 weeks for 4 cycles. After NAC the pts underwent surgery and were assessed for pathologic response. All pts received postoperative Radiotherapy. Results: pCR that was defined as no residual invasive tumor in both the breast and axilla was reported in 16 (84%) of the cases. The other 3 pts achieved Partial Response (PR). After a median follow-up of 24 months (5-41 months) 3 pts have recurred, 2 with PR and 1 with pCR. Both of the pts with PR that recurred have dead. Conclusions: This regimen of NAC resulted in a very high pCR in pts with LATNBC, an indicator associated with a better survival outcome of this highly lethal disease.
In vitro assessment of the inflammatory breast cancer cell line SUM 149: Discovery of two single nucleotide polymorphisms in the RNase L gene.
Authors: B. T. Nokes, H. Cunliffe, A. R. Brown, G. R. Sheth, A. Stopeck, R. B. Livingston, B. W. Futscher, J. E. Lang
Journal: Journal of Clinical Oncology (2011)

196 Background: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer, accounting for 5% of breast cancers diagnosed annually in the United States. Understanding the distinct biology of IBC could help provide novel treatment targets. We sought to evaluate whether or not the IBC cell lines SUM 149 and SUM 190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We also performed proliferation assays; developed dose response curves to assess the treatment effect of interferon-alpha (IFN-a); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated but not definitively associated with IBC,) in the DNA and RNA of SUM 149 cells. Results: According to our allelic discrimination SNP assay, 2/2 IBC cell lines were homozygous for the 462 and 541 variants, whereas 0/10 non-IBC cell lines were homozygous positive for the 462 variant (p = 0.015) and 2/10 non-IBC cell lines contained homozygous alleles for the 541 variant (p = 0.52). We also found a dose and time-dependent decrease in the proliferation of SUM 149 IBC cells treated with IFN-a. In contrast, non-IBC cell lines did not show a dose-response decrease in cell proliferation. Our reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis for the env/LTR and late LTR sequences of the putative HMTV revealed no evidence of the putative viral genome. Conclusions: We discovered 2 SNPs, in the 462 and 541 variants of the RNase L gene, that were homozygously mutated in IBC cell lines but the 462 variant was absent in non-IBC lines. Our discovery of these mutated SNPs present in IBC cell lines suggests a possible genetic risk factor for IBC. In our study, the IBC cell line SUM 149 demonstrated a direct and specific response to treatment with IFN-a, an antiviral agent. We noted no evidence of HMTV infection in that cell line. Further studies of the prevalence and significance of the RNase L 462 and 541 variants in human IBC tissue specimens are warranted to validate our in vitro findings.
Endogenous Nras G12D/+ and G12D/G12D Distinctly Regulate Self-Renewal and Differentiation of Haematopoietic Stem Cells
Authors: Guangyao Kong, Jinyong Wang, Yangang Liu, Juan Du, Alisa Damnernsawad, Erik A. Ranheim, Myung-Jeom Ryu, Jing Zhang
Journal: Blood (2012)
Busulfan Area-under-the-Curve Finding Study within a Busulfan/Fludarabine (BuFlu) Conditioning Regimen before Allogeneic Hematopoietic Cell Transplantation (HCT).
Authors: Teresa Field, Janelle Perkins, Melissa Alsina, Ernesto Ayala, Karen Fancher, Hugo F. Fernandez, Dawn Garrett, William Janssen, Mohamed Kharfan-Dabaja, Lia Perez, Daniel Sullivan, Cheryl Tate, Claudio Anasetti
Journal: Blood (2006)
Overexpression of Calr Mutants Perturbs Developmental Hematopoiesis in Zebrafish Embryos
Authors: Ken-Hong Lim, Yu-Cheng Chang, Yi-Hao Chiang, Huan-Chau Lin, Chiao-Yi Chang, Ching-Sung Lin, Ling Huang, Wei-Ting Wang, Caleb Gon-Shen Chen, Wen-Chien Chou, Yuan-Yeh Kuo
Journal: Blood (2016)