tbuckley/cabot-search huggingface dataset:
Maintenance pemetrexed (Pem) plus best supportive care (BSC) versus placebo (Plac) plus BSC: A randomized phase III study in advanced non-small cell lung cancer (NSCLC)
Authors: C. P. Belani, T. Brodowicz, T. Ciuleanu, J. H. Kim, M. Krzakowski, E. Laack, Y. L. Wu, P. Peterson, K. Krejcy, C. Zielinski
Journal: Journal of Clinical Oncology (2009)

CRA8000 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
Impaired mTORC1-Dependent Expression of Homer-3 Influences SCA1 Pathophysiology
Authors: Céline Ruegsegger, David M. Stucki, Silvio Steiner, Nico Angliker, Julika Radecke, Eva Keller, Benoît Zuber, Markus A. Rüegg, Smita Saxena
Journal: Neuron (2016)
Marrow cell genetic phenotype change induced by human lung cancer cells
Authors: P. J. Quesenberry, M. Del Tatto, D. Berz, T. Miner, T. Ng, E. S. Winer, J. Aliotta, G. Colvin, M. Dooner, G. Dooner, J. P. Fontaine
Journal: Journal of Clinical Oncology (2009)

11108 Background: Murine lung-derived microvesicles are capable of inducing lung-specific mRNA in marrow cells, when co-cultured across from these cells, but separated from them by a cell-impermeable (0.4 micron) membrane. These converted murine marrow cells showed mRNA elevations, lung-specific protein production and enhanced capacity to convert to lung epithelial cells after in vivo transplantation into irradiated mice. We examine here whether fresh tissue from lung cancer patients would have the same capacity to genetically alter co-cultured human marrow cells. Methods: Lung cancer samples were collected from 5 patients undergoing surgery. Minced tumor tissue at 50–100 mg was co-cultured in a semi-permeable culture plate insert opposite 3.0 ×10 6 human marrow cells. The marrow cells were harvested after 2–7 days of co-culture. Marrow cell RNA was analyzed for lung specific mRNA using real time RT-PCR. Relative levels of gene expression was expressed a fold increase compared to level in controls. Results: Lung cancers studied were adenocarcinoma, endobronchial alveolar carcinoma, bronchioloalveolar carcinoma, non-small cell carcinoma and squamous cell carcinoma. mRNAs for aquaporin 1–5, specific for type I pneumocytes and surfactant A-D, specific for type II pneumocytes, were measured. Aquaporin I was elevated in marrow cells from co culture with all lung cancers; elevations ranging from 2.15 to 56.7 fold (mean 23 fold). Similarly surfactant B mRNA was induced in marrow cells by all lung cancers with fold elevations ranging from 7.9 to 2164 (mean fold elevation 668). More variable elevations were also seen with aquaporin 3, 4, and 5, surfactant A, surfactant C, and surfactant D. Ultracentrifugation (28,000 g) of conditioned media from these cancers revealed the presence of microvesicles with diameters of 100–180 nm. Conclusions: These observations indicate that the genetic phenotype of cells in the vicinity of lung cancer cells can be altered and that these alterations might be mediated by microvesicle transfer of genetic information. No significant financial relationships to disclose.
Optimization of Postremission Therapy in Follicular Lymphoma: Efficacy of Rituximab Maintenance
Authors: Rupali Roy, Leo I. Gordon
Journal: Journal of the National Comprehensive Cancer Network (2011)

Rituximab has been proven to be an important part of the treatment of newly diagnosed and relapsed or refractory follicular lymphoma both alone and in combination with chemotherapy. Given its tolerability, rituximab has now been investigated in the maintenance setting in an effort to further improve progression-free and overall survival in patients with follicular lymphoma.
Phase I study of CYT997, a novel cytotoxic and vascular disrupting agent, given as a 24-hour intravenous infusion to patients with advanced solid tumours
Authors: J. Lickliter, G. Smith, M. Burge, A. Coulthard, D. Wyld, A. Wilks, P. Vasey
Journal: Journal of Clinical Oncology (2007)

14115 Background: CYT997 is a novel tubulin-binding small molecule which inhibits microtubule assembly and also demonstrates potent vascular-disrupting activity in preclinical tumour models. Methods: CYT997 was administered by continuous infusion over 24 hours every 3 weeks to patients with advanced cancer. Dose escalation proceeded by a standard phase I design (3 patients per dose level) for the first 18 patients; subsequently, an accelerated titration design (1 patient per dose level) was utilized. Intrapatient dose escalation was permitted. Pharmacokinetic (PK) analyses were performed in the first cycle. Tumour response was determined every second cycle using RECIST criteria. Pharmacodynamic effects on the tumour vasculature were assessed with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: 22 patients (M/F: 11/11; median age 57.5, range 28–75) were enrolled with tumour types including melanoma (4), renal cell (4), colorectal (2), non-small cell lung (2) and adenoid cystic (2) carcinomas, mesothelioma (2) and others (6). A total of 66 cycles of CYT997 were administered (median 2/patient, range 1–6) over 10 dose levels (7, 14, 23, 35, 49, 65, 86, 114, 152 and 202 mg/m 2 ). No dose-limiting toxicity was observed. Because of grade-2 injection site reactions in 2 patients (one each at dose levels 3 and 4), all subsequent patients received CYT997 via a central venous access device. Other toxicities included grade-2 renal toxicity at dose- level 8 in one patient with abnormal baseline renal function and grade-1 QT c prolongation in one patient at dose-level 10. No myelosuppression, gastrointestinal toxicity or clinically-significant cardiac toxicity were observed. PK data revealed dose-related increases in C max and AUC values. Six patients had stable disease after 4 cycles of CYT997. Conclusions: CYT997 was well tolerated at the doses studied and accrual to the 269 mg/m 2 dose level will now proceed. No significant financial relationships to disclose.
A small-molecule antivirulence agent for treating <i>Clostridium difficile</i> infection
Authors: Kristina Oresic Bender, Megan Garland, Jessica A. Ferreyra, Andrew J. Hryckowian, Matthew A. Child, Aaron W. Puri, David E. Solow-Cordero, Steven K. Higginbottom, Ehud Segal, Niaz Banaei, Aimee Shen, Justin L. Sonnenburg, Matthew Bogyo
Journal: Science Translational Medicine (2015)

A high-throughput screen against the Clostridium difficile toxin B cysteine protease domain identified a drug in clinical trials that reduced C. difficile pathology in a mouse model.
Intensive chemotherapy, total body irradiation, and autologous marrow transplantation for chronic granulocytic leukemia-blast phase: report of four additional cases.
Authors: G L Phillips, G P Herzig
Journal: Journal of Clinical Oncology (1984)

Four patients with Philadelphia chromosome (Ph1)-positive chronic granulocytic leukemia (CGL) in blast phase received cyclophosphamide, total body irradiation, and autologous marrow transplants using cryopreserved marrow from the stable phase. Two patients fully reestablished stable-phase leukemia that lasted for 26 and six months; the first patient developed transient Ph1-negative hematopoiesis after transplantation. Three patients eventually died of recurrent blast-phase leukemia. Previous studies using autologous marrow for CGL have reported an occasional long survivor, but incomplete engraftment and especially the rapid recurrence of blast-phase leukemia have been responsible for the overall poor results. The latter problem complicates even normal marrow transplantation, indicating the inadequacy of the current therapeutic regimens used for treating blast-phase leukemia and the possibility of improving results with more effective regimens and autologous marrow transplantation. Although it is unknown whether the reestablishment of Ph1-negative hematopoiesis after transplantation contributes to improved survival, this interesting phenomenon must be investigated further.
Striatal Reward Activity and Antipsychotic-Associated Weight Change in Patients With Schizophrenia Undergoing Initial Treatment
Authors: Mette Ø. Nielsen, Egill Rostrup, Sanne Wulff, Birte Glenthøj, Bjørn H. Ebdrup
Journal: JAMA Psychiatry (2016)

Weight gain is a common and serious adverse effect of antipsychotic treatment. A variable individual predisposition to development of metabolic disturbances calls for predictive biological markers.To investigate whether attenuated striatal activity during reward anticipation is associated with amisulpride-induced weight change in antipsychotic-naive patients with schizophrenia undergoing initial treatment and to examine the association between weight change and changes in reward anticipation activity after treatment.Sixty-nine antipsychotic-naive inpatients and outpatients with schizophrenia were included in a multimodal longitudinal cohort study from December 16, 2008, to December 11, 2013. Fifty-eight patients underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. After 6 weeks of treatment with amisulpride, a relatively selective dopamine D2 antagonist, 39 patients underwent a second fMRI scan and measurement of change in body weight. Final follow-up was completed on January 14, 2014, and data were analyzed from October 25, 2014, to June 15, 2015 and August 31 to September 19, 2015.Six weeks of individually dosed amisulpride treatment.Reward-anticipation activity in the striatum before and after treatment and weight change.Of the 69 patients who consented to the study, 39 underwent the follow-up fMRI and weight measurement (age range, 18-45 years; 17 women and 22 men). The mean (SD) daily dose of amisulpride was 272 (168; range, 50-800) mg, and patients gained a mean (SD) of 2.3 (2.8; range, -4 to 8) kg in body weight. Improvement from baseline to follow-up was found on the mean (SD) positive (19.9 [4.1] to 14.3 [3.8]), general (39.7 [7.7] to 30.5 [7.7]), and total (78.5 [15.3] to 63.2 [13.9]) scores on the Positive and Negative Syndrome Scale (P < .001). Weight gain was predicted by low mean (SD) baseline reward-related activity in the right-sided putamen (0.20 [0.93]; F35,3 = 5.64; P = .003). After 6 weeks, weight gain was associated with an increase in mean (SD) reward activity in the same region during treatment (0.28 [0.74]; F37,1 = 4.48; P = .04).Activity in striatal regions of the reward system appears to be associated with the individual variability in the predisposition for antipsychotic-associated weight gain. Moreover, pharmacologic modulation of the reward system may play a role in antipsychotic-associated weight gain.
Establishment of a predictive classifier of node-positive breast cancer patients treated by FEC100 chemotherapy using gene expression profiling
Authors: M. Campone, C. Charbonnel, F. Magrangeas, S. Minvielle, J. Genève, A. Martin, R. Deporte, R. Bataille, L. Campion, P. Jézéquel
Journal: Journal of Clinical Oncology (2006)

13004 Background: In breast cancer treatment, biomarkers providing information about chemotherapy sensitivity are needed. FEC100 combination, frequently prescribed in Europe, is still applied empirically to patients. Our study’s goal was to establish a classifier of sensitivity to this regimen using gene expression data and classical clinicopathologic parameters. Methods: The study retrospectively included 151 patients belonging to the FEC100 arms of two multicentric phase III clinical trials: PACS01 (n = 128) and PEGASE01 (n = 23) (FNCLCC). Patients had unilateral breast cancer, showed no evidence of distant metastasis, were node-positive, aged less than 65-year-old. Median follow-up was 5 years. The number of relapses were respectively 23 and 10. We used cDNA nylon microarrays containing 7,000 genes to analyze gene expression profiles of tumor. Patients were split into a training set and a test set. A 3-step analysis based on Cox regression was applied: 1) elimination of non discriminant genes, 2) robust (resampling) univariate selection of discriminant genes and 3) development of multivariate models combining the discriminant genes, the Nottingham Prognostic Index (NPI) (developed in 2 binary variables) and the hormonal receptors. As a final step, after dichotomization of the retained genes, a risk score was built and applied first on the test set, and then on the whole cohort. Kaplan-Meier curves and logrank tests were performed to assess the new risk score. Results: The new risk score (one gene [G6224] and NPI) permitted to separate patients from the test set in 3 significantly different groups; it was also an improvement on NPI (test set: NPI, p = 0.0005; risk score p = 0.0001 - whole cohort: NPI, p = 2.10 −5 ; risk score, p = 1.10 −10 ). Conclusions: We identified G6224 whose expression combined with NPI showed a good capacity for classifying breast cancer patients who received FEC100 chemotherapy. Our results strengthen the interest of G6224 since it was previously described in various solid tumors as a prognostic biomarker with a tumor-suppressor activity. No significant financial relationships to disclose.
Antitumor Activities Of An Oral Selective HSP90α/β Inhibitor, TAS-116, In Combination With Bortezomib In Multiple Myeloma
Authors: Rikio Suzuki, Teru Hideshima, Shuichi Ohkubo, Naoya Mimura, Jiro Minami, Hiroto Ohguchi, Shohei Kikuchi, Diana D. Cirstea, Francesca Cottini, Dharminder Chauhan, Paul G. Richardson, Nikhil C. Munshi, Teruhiro Utsugi, Kenneth C. Anderson
Journal: Blood (2013)
Computed tomography of the chest as a way to diagnose and monitor treatment of patients with sarcoidosis in Omsk, Russian Federation
Authors: Dmitriy Petrov, Nikolay Ovsyannikov, Vadim Gershevich
Journal: European Respiratory Journal (2011)

Purpose: To evaluate lung injuries with computed tomography (CT) for diagnosis and therapeutic follow-up of patients with sarcoidosis (S).

Methods: 247 consecutive patients with biopsy-proven S were retrospectively included respectively. All patients underwent corticosteroid (CS) treatment. All patients were re-examined by CT to assess response to CS treatment at 3 and 6 months.

Results: Mediastinal lymphadenopathy (ML) was detected in 93.75%. The small focal dissemination (SFD) detected in 67,5% and frosted glass areas (FGA) - 30%. A single large-scale patchy shadows (SLPS) - 8,75%, the consolidation of lung tissue (CLT) - 6,25%, bronchiectasis - 3,75%, pleural effusion - 1,25%. The ML in stage I S was detected in 100%. Bilateral intrathoracic lymph nodes (LN) lesions sometimes asymmetrical observed in 29.7%. Bronchopulmonary LN injury in 86,7%. Stage II S manifested as 100% of symmetrical ML, SFD - 89%, the presence of FGA - 37,3% (p = 0,001). Rarely detected SLPS - 11,8%, the CLT - 8,7%, pleural effusion was observed in isolated cases. After 3 and 6 months of CS treatment the decrease ML was detected in 35%. The SFD disappeared in 13.7% after 3 months of treatment and in 44% after 6 months of therapy. FGA remained at 100% within 3 months of therapy, but after 6 months of treatment with CS disappeared or decreased in size in 7.3%.

Conclusion: The most frequent CT manifestations of S were ML, a syndrome of small focal dissemination syndrome and frosted glass. The effectiveness of glucocorticoid therapy in patients with S is confirmed by CT of the thorax, which shows the disappearance or reduction of CT manifestations in respiratory organs.
George Nicholas Papanicolaou (1883-1962)
Authors: P R Broso, G Buffetti
Journal: CA A Cancer Journal for Clinicians (1973)

G. N. Papanicolaou was born on May the 13, 1883 in the city of Kymi on the Greek island of Euboea. He received his MD degree from the University of Athens in 1904 and a PhD from the University of Munich in 1910. After service as a medical officer in the Balkan War of 1912-1913, he came to New York with Mary (for over 50 years Dr Pap's life companion). George's violin playing at restaurants and coffee-shops supplied them with a few extra cents. Papanicolaou was appointed assistant in the Pathology Laboratory at the New York Hospital. In 1928 he presented his work "New Cancer Diagnosis" to the third race betterment conference (Battle Creek, Michigan). But the work was met with scepticism. The now famous monograph "The Diagnostic Value of Vaginal Smears in Carcinoma of the Uterus" was published in 1941 in the Am J Obst Gyn. During this time, he developed his method of preservation of these cells by wet fixation and precise staining. Papanicolaou persisted with his ideas, and finally cytologic examination of the cervix was accepted. The power of Papanicolaou screening for uterine cancer was remarkable. The first National Cytology Congress, held in 1948, hailed this new diagnostic tool for carcinoma of the cervix as unique because it could detect cancer before it was visible. He described the importance of a distinct cellular pattern corresponding to cervical intraepithelial neoplastic lesions. The value of this pattern, expressing evolutionary steps in the development of cancer at individual cell levels, was not appreciated.(ABSTRACT TRUNCATED AT 250 WORDS)
S0124: A randomized phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated extensive stage small cell lung cancer (E-SCLC)
Authors: R. B. Natale, P. N. Lara, K. Chansky, J. J. Crowley, J. R. Jett, J. E. Carleton, J. P. Kuebler, H. J. Lenz, P. C. Mack, D. G. Gandara
Journal: Journal of Clinical Oncology (2008)

7512 Background: The role of irinotecan in SCLC remains controversial. Although J9511 demonstrated a significant survival benefit for IP over EP in Japanese pts with E-SCLC (Noda, et al. NEJM 2002), another small phase III trial did not (Hanna, et al JCO 2006). S0124 was designed to confirm the results of J9511 in a North American & to investigate the association of genetic polymorphisms (SNPs) with outcomes. Methods: Pts with documented E-SCLC, adequate end-organ function & controlled or no brain metastases were stratified by single vs multiple metastases, normal vs elevated LDH, & weight loss ≤ 5% vs > 5%, & randomized to (IP) I-60 mg/m2 days 1, 8, & 15 + P-60 mg/m2 day 1, Q 4 weeks or (IP) E-100 mg/m2 days 1–3 + P-80 mg/m2 day 1, Q 3 weeks. A blood specimen for SNP analysis was collected pre- randomization. Results: From 11/02 through 3/07, 671 pts were accrued, with 645 eligible: IP (N=323) & EP (N=322). Pt demographics: median age 63, 57% males, 76% with multiple metastatic sites, 62% ≤ 5% weight loss. Grade 3 + 4 toxicities in IP vs EP: neutropenia = 33% vs 64%, thrombocytopenia = 3.5% vs 14%, diarrhea = 19% vs 3%, infection = 12% vs 18%, cardiovascular = 11% vs 12%, renal = 3.8% vs 3.8% & hepatic = 2% vs 5%. There were 12 treatment related deaths on IP & 8 on EP. Efficacy data are summarized in the table below. SNPs, ABCBq*3435 T/T & UGT1A1*3156 A/A, were associated with an increased risk of grade 3+ diarrhea (p=.04) and neutropenia (p=.009), respectively, for IP, as previously described (Lara, ASCO 2007). Updated results will be presented. Conclusions: This large randomized trial failed to confirm the positive results of J9511. IP & EP produced comparable overall response rates & survival outcomes with less hematologic & greater gastrointestinal toxicity with IP compared to EP. EP remains the standard of care for ESCLC in North American pts. Population-related differences in pharmacogenomics may explain the divergent results of J9511 & S0124. NIH CA32102 Outcome IP EP Response (CR + PR) 4% + 55% = 59% 1% + 54% = 55% PFS (months) 5.7* 5.2* OS (months) 9.7 8.9 % 1 Year Survival 39% 33% * (p = .03) No significant financial relationships to disclose.
Abstract 366: A novel transcript variant of androgen receptor identified in circulating tumor cells from castration-resistant prostate cancer patients as a potentially prognostic biomarker
Authors: Zhigang Kang, Avani Shah, Yunkai Yu, Yuelin Zhu, Ali Asgar Bhagat, Kyra Zhao, Andrew Wu, James Gao, Ravi Madan, James Gulley, William Dahut, Paul Meltzer, Liang Cao
Journal: Cancer Research (2015)

Abstract Circulating tumor cells (CTCs) are rare cancer cells in the bloodstream thought to have a key role in cancer metastasis. There are enormous interests in their analysis for castration-resistant prostate cancer (CRPC) due to their tendency to metastasize to bone. In this study, we applied a surface marker-independent microfluidic device for CTCs capture and retrieval that is based on cell size and deformability. Our device was able to capture 90% and recover 30% of tumor cells in spike experiments. We also developed and validated assays capable of detecting the transcript levels of selected molecular markers in single cells prepared with C1TM Single-Cell AutoPrep System. Blood samples drawn from 34 CRPC patients and 10 primary prostate cancer patients (PPC) were preceded for CTC isolation and molecular characterization. We found that 73% CRPC patients and 10% PPC patients were positive for EpCAM, and only about half of the EpCAM-positive CRPC cases were PSA or AR positive. It is interesting that while there is a strong association between AR and PSA expression in CTC samples, there is no correlation between AR or PSA transcripts in CTCs and serum PSA protein levels in CRPC patients. The positive detection of AR or PSA, but not EpCAM is statistically associated with poor prognosis of the CRPC patients. Very intriguingly, we identified a novel androgen receptor (AR) transcript variant -ARv from four CRPC patients’ CTCs. This ARv lacks a 554bp sequence region in the ligand binding domain (LBD), resulting in a loss of the entire LBD. Clinical data analysis revealed that the ARv is significantly associated with worse survival of CRPC patients (p&amp;lt;0.0001). In vitro functional studies showed this novel ARv is constitutively active in the absence of testosterone. Our findings suggest that this AR variant might contribute to the late stage progression of the diseases and could be used as a potential indicator for alternative therapies. In summary, our new fluidic device is capable of isolating CTC to enable molecular marker analysis, providing value in prognosis and guidance to therapy. Citation Format: Zhigang Kang, Avani Shah, Yunkai Yu, Yuelin Zhu, Ali Asgar Bhagat, Kyra Zhao, Andrew Wu, James Gao, Ravi Madan, James Gulley, William Dahut, Paul Meltzer, Liang Cao. A novel transcript variant of androgen receptor identified in circulating tumor cells from castration-resistant prostate cancer patients as a potentially prognostic biomarker. [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 366. doi:10.1158/1538-7445.AM2015-366