tbuckley/cabot-search huggingface dataset:
Abstract 425: Induced Pluripotent Stem Cell Derived Cardiomyocyte Tissue Engineered Scaffold Improves Left Ventricular Function and Electro-Mechanical Coupling in Rats with Heart Failure
Authors: Jordan J Lancaster, Elizabeth Juneman, Pablo Sanchez, Kyle Weigand, Talal Moukabary, Nicole Lahood, Amitabh Pandey, Joseph J Bahl, Steven Goldman
Journal: Circulation Research (2015)

Background: Chronic Heart Failure (CHF) is the leading cause of hospital readmissions in the United States. It may result from systolic or diastolic dysfunction, which often coexists. Here we report the effects of delivering human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) via a bioengineered patch on left ventricular function in rats with CHF. Methods: Adult male Sprague-Dawley rats underwent left coronary artery ligation and were randomized to Sham, CHF, and hiPSC-CM patch. High purity human hiPSC-CMs were obtained from Cellular Dynamics International, seeded and co-cultured onto a vicryl matrix embedded with human dermal fibroblasts. Echocardiography was performed at 3 and 6 weeks post-randomization. Hemodynamic pressure measurements were performed at 6 weeks post-ligation with Millar solid state micromanometer catheters. Open chest Electrophysiologic (EP) mapping was performed at 6 weeks post ligation. Results: Patches constructed with hiPSC-CMs displayed synchronized and spontaneous contractions within 48hrs of culture which developed in robustness over time. At maximal robustness, contractions were visualized across the full thickness of the construct. Contractions were recorded at 36+5 beats BPM. Three weeks after implantation, the hiPSC-CM patch decreased LV EDP (45%), Tau (29%), E/e’ (23%) and increased, EF (14%), e’ (20%), and e’/a’ (36%) versus CHF. EP studies show electro-mechanical coupling between the patch and the native myocardium with normal activation through the patch and increases (P&lt;0.05) voltage amplitude in CHF versus hiPSC-CM patch treated rats (1±0.5 mV vs 6±1.5mV). Conclusion: Cardiac patch implantation with human iPSC derived cardiomyocytes is an effective and feasible method of treating CHF with improvements in systolic function, diastolic function, and electro-mechanical coupling in rats with CHF.
Impaired Clonogenic Capacity Contributes to Bone Marrow Hypoplasia and Late Hematological Recovery after Zevalin in the Low-Grade NHL Patients.
Authors: Wojciech Jurczak, Marta Szostek, Zbigniew Rudzki, Dorota Krochmalczyk, Joanna Wegrzyn, Jaroslaw Czyz, Aleksander B. Skotnicki
Journal: Blood (2004)
Perioperative immuno-modulation with interleukin-2 (IL-2) in patients with renal cancer: long-term outcome
Authors: T. Klatte, A. Ittenson, F.-W. Röhl, M. Ecke, E. P. Allhoff, M. Böhm
Journal: Journal of Clinical Oncology (2005)

4601 Background: Complex perioperative immuno-dysfunction occurs in patients with renal cell carcinoma undergoing surgery, which can be effectively modulated by pretreatment with IL-2. Methods: Of 108 patients who underwent tumour nephrectomy, 54 patients received 4 doses of 10 Mio IE per m2 interleukin-2 (IL-2) q12h s.c. a week before operation followed by a maintainance dose of 3 Mio IE per m2 until a day before the operation. 54 matched patients did not receive IL-2. Parameters of cellular and humoral immunity (differential blood count, markers of T-cells CD3, CD4, and CD8, T-cell activation CD6, and CD28, B-cells CD19, monocytes CD14, NK-cells CD16, CD56, and CD57, and activation markers CD25, CD69, and HLA-DR) were measured in peripheral venous blood before and during IL-2, one day before and immediately after the operation, and on the 1., 3., 5., and 10. postoperative day. The end point of interest was tumour-specific survival time. Survival distributions were estimated with the Kaplan-Meier Method: The relationship between survival and each of the variables was analysed with the log-rank test for categorical variables. Results: Patients’ groups did not differ with respect to age, sex, tumour stage and grade, operation time, operative technique, and intraoperative blood loss. IL-2 related toxicity was WHO grade I (24.1%), II (68.5%), and III (7.4%). All patients showed postoperatively elevated leukocyte and granulocyte counts. T-cell and activation markers were decreased. However, all these alterations were significantly less accentuated in patients who had been pretreated with IL-2. Tumour specific survival was better in pretreated patients (95.5% vs. 79.6% after 1 yr., 86.5% vs. 77,6% after 2 yrs., p<0.02) after a mean follow-up of 25 vs. 45 months. Patients with advanced tumours (UICC=4) benefited most (33.3% vs. 14,3% after 2 yrs., p<0.002). Conclusions: Pretreatment with IL-2 modulates perioperative immuno-dysfunction in patients undergoing tumour nephrectomy, thus complementing surgery. This affects in particular T-cell mediated immunity. Acceptable toxicity affords a significant survival benefit, in particular in patients with advanced tumours. No significant financial relationships to disclose.
Levels of sIL-2R in Sera Depend On Number of CD25-Positive Lymphoma Cells and MMP-9-Positive Macrophages in DLBCL.
Authors: Noriaki Yoshida, Akira Sakai, Yoshiko Okikawa, Yuta Katayama, Hideki Asaoku, Hirotaka Matsui, Koji Arihiro, Megumu Fujihara, Takashi Nishisaka, Naomi Sasaki, Yoshito Sadahira, Akiro Kimura
Journal: Blood (2009)
Abstract O.45: Kawasaki Disease Refractory To Primary IVIG Treatment - Use Of Scoring Systems And Predictive Modelling Based On Data From Singapore Children
Authors: Swee Chye Quek, Yao Guang Leow, Dimple D Rajgor, Terence Lim, Chew Kiat Heng, Robert Grignani
Journal: Circulation (2015)

Objectives: Although first-line treatment for Kawasaki Disease (KD) is IVIG, some children may not respond, requiring repeat IVIG or another second-line therapy. It is important to predict non-responders for timely management decisions in this group of patients. The objective of our study was to assess the predictive value of the currently available scoring systems and propose an improved model for predicting refractory KD, based on data from KD patients in Singapore. Method: We performed a retrospective review of the medical records (2001-2014) of 180 children with KD and identified 17 refractory cases. The 4 scoring systems; Egami, Kobayashi, Sano and Fukunishi; were applied to the data of refractory KD cohort to determine their predictive value based on sensitivities (SN) and specificities (SP). A logistic regression model was built using 5 predictors (age, AST, CRP, Hb, platelet and duration of illness) which were common among the existing models to propose a new scoring system based on our data -. The formula used was 1/(1+e^(-(-5.642839-0.192452*(zHb)-0.011597*(Age)+0.003756*(PLT)+0.009441*(CRP)+0.006015*(AST)+0.084408*(Days). Results: The SN and SP obtained were; (1) Egami: SN 35.3%, SP 73.9% (original SN 78% and SP 76%) (2) Kobayashi: SN 23.5%, SP 67.5% (original SN 86% and SP 68%) (3) Sano: SN 18.8% and SP 88.2% (original SN 77% and SP 86%) (4) Fukunishi: SN 53.3% and SP 76.0% (original 84.6% and 87.0%). As the existing scoring systems proved less predictive in our population, we used logistic regression model to derive a formula incorporating the common variables to predict the likelihood of non-responders. This model attained an SN of 80% and SP of 80%. Conclusion: The proposed model should be validated prospectively in our local population for predicting unresponsiveness, and the formula can be applied to different datasets from other KD populations to test its robustness.
Predicting survival in stomach cancer: The role of quality-of-life assessment.
Authors: Donald Peter Braun, Digant Gupta, Edgar Donald Staren
Journal: Journal of Clinical Oncology (2013)

100 Background: Although assessment of quality of life (QoL) with validated instruments has been increasing in the clinical oncology community, there is little data examining its prognostic significance in stomach cancer. We investigated the association between baseline QoL and survival in stomach cancer. Methods: A consecutive case series of 129 stomach cancer patients treated between Jan 2001 and Dec 2009. QoL was evaluated at baseline using EORTC-QLQ-C30 which incorporates 1 global, 5 functional and 8 symptom scales. Scores range from 0-100 with higher scores in global/functional scales and lower scores in symptom scales indicating better QoL. Patient survival was defined as the time between the date of first patient visit and the date of death from any cause/date of last contact. Cox regression was performed to evaluate the prognostic significance of QoL. Results: Mean age at diagnosis was 60.9 years. 61 patients were newly diagnosed and received their first cancer treatment at our hospital, while 68 were previously treated elsewhere. Stage at diagnosis was I, 12; II, 11; III, 17; and IV, 89. Median overall survival was 8.4 months (95% CI: 5.9-10.7 months). QoL scales predictive of survival upon univariate analysis were global (p=0.001), physical (p=0.002) and fatigue (p=0.02). Upon multivariate analyses, after adjusting for age, gender, stage, and treatment history, global (HR=0.84; 95%CI=0.74, 0.93; p=0.001), physical (HR=0.83; 95%CI=0.73, 0.93; p=0.001) and fatigue (HR=1.10; 95%CI=1.02, 1.18; p=0.02) scales were significantly associated with survival, such that patients with higher (better) global and physical scores and lower (better) fatigue scores had better survival. For both newly diagnosed and previously treated patients, global and physical scales were significantly predictive of survival. Conclusions: Baseline QoL elements that reflect specific functional and symptomatic attributes provide useful prognostic information in stomach cancer. Significantly, this held true for global and physical function for both newly diagnosed and previously treated patients. Such determinations should be considered when designing clinical trials with survival endpoints and may aid decision-making in clinical practice.
Association of declining PSA values with a lower risk of progression in the Canary Prostate Cancer Active Surveillance Study (PASS).
Authors: James D. Brooks, Elissa C. Brown, Matthew R. Cooperberg, Lisa F. Newcomb, Peter Carroll, Ziding Feng, Martin Edwin Gleave, Raymond Lance, Martin G. Sanda, Ian Murchie Thompson, John Thomas Wei, Peter Nelson, Daniel W. Lin
Journal: Journal of Clinical Oncology (2013)

88 Background: Active Surveillance of men with low risk prostate cancer entails uncertainty for the patient and physician in determining risk of progression. While PSA determinations are frequently measured in men on active surveillance, no study thus far has found PSA velocity (PSAV) or PSA doubling times that identify patients at risk for clinical progression. However, based on observations in PASS, we hypothesized that men with negative PSAV might be at decreased risk for progression. Methods: From 723 PASS participants, we identified 396 who had at least 5 PSA values over 12-24 months after their diagnosis and prior to progression or last follow-up. Of the 396 patients, 56 progressed as defined by increase in Gleason score or increase in tumor involvement of the core biopsies to ≥ 34%, or increase in clinical stage while 340 men had no progression. PSAV is the slope of the log(PSA) values over time. ROC analysis was used with PSAV as the predictor of biopsy/clinical progression. Results: PSAV was mildly associated with clinical/biopsy progression with an AUC of 0.62 (95% CI: 0.54-0.70). Interestingly, by thresholding PSAV at 0, 150 of 396 men had negative a PSAV. Subjects with with a negative PSAV had a much lower rate of progression while on active surveillance. PSAV&lt;0 had a negative predictive value for progression of 0.93 (95% CI: 0.88-0.97). The progression rate for those with negative PSA velocity was 11/150 ≈ 0.07, or 7% and 18% (45/246) for those with positive PSA velocity. Viewed another way, men with PSAV&lt;0 had a 0.4 fold relative risk of progression compared to men with a positive PSAV or were 60% less likely to have clinical/grade progression than those with positive PSA velocity (95% CI: 0.21-0.75). Conclusions: Declining PSAV in men on active surveillance for clinically localized prostate cancer is associated with a lower risk of clinical progression. Clinical trial information: NCT00756665.
Outcomes of adjuvant radiotherapy and lymph node dissection in elderly patients with pancreatic cancer treated with surgery and chemotherapy.
Authors: Jessica Freilich, Eric Albert Mellon, Gregory M. Springett, Ken Meredith, Pamela Joy Hodul, Mokenge Peter Malafa, William J. Fulp, Xiuhua Zhao, Sarah E. Hoffe, Ravi Shridhar
Journal: Journal of Clinical Oncology (2014)

332 Background: To determine the effects of postoperative radiation therapy (PORT) and lymph node resection (LNR) on survival in patients age ≥ 70 with pancreatic cancer treated with surgery and chemotherapy. Methods: An analysis of patients with surgically resected pancreatic cancer who received chemotherapy from the SEER database from 2004-2008 was performed to determine association of PORT and LNR on survival. Survival curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. Results: We identified 961 patients who met inclusion criteria. The only significant difference between PORT patients and no PORT patients was age, median 75 and 76 years, respectively (p=0.007). Overall survival (OS) in PORT versus no PORT was not statistically different in the whole cohort (p=0.064), N0 (p=0.803) or N1 (p=0.0501). On univariate analysis (UVA) there was increased OS in patients with lower T stage (p&lt;0.001), N0 status (p&lt;0.001), lower AJCC stage (p&lt;0.001) and lower grade (p&lt;0.001). No OS difference was seen based on gender, location, or PORT. There was no difference in OS based on number of lymph nodes removed in all patients (p=0.74), N0 (p=0.59), and N1 (p=0.07). MVA for all patients revealed higher T stage, N1, and high grade were prognostic for worse mortality, while there was a trend for decreased mortality with PORT (p=0.052). In N0 patients, increased T-stage and grade were prognostic for worse survival, while PORT and number of lymph nodes removed were not. In N1 patients, higher T-stage and grade were prognostic for increased mortality, while increasing number of lymph nodes removed was associated with decreased mortality. PORT trended towards improved survival in N1 patients (p=0.06). Age, gender and tumor location were not prognostic for survival. Conclusions: Adjuvant radiation therapy and number of lymph nodes removed in patients age ≥70 does not seem to correlate with increased OS in surgically resected pancreatic cancer treated with chemotherapy. Future clinical trials will need to address age as a stratification factor for pancreatic cancer in the adjuvant setting.
First results of a phase II study of bevacizumab in combination with trastuzumab and capecitabine as first-line treatment of HER2+ LA/MBC.
Authors: S. Tjulandin, A. Makhson, J. Gligorov, M. Lichinitser, A. Lluch, V. Semiglazov, N. Scotto, L. Mitchell, M. Martin
Journal: Journal of Clinical Oncology (2011)

571 Background: Based on established clinical activity and potential synergism of trastuzumab (H), bevacizumab (A) and capecitabine (X) in MBC, this single-arm, open-label study (MO21926) evaluated the H + A + X combination as first-line therapy for HER2+ LA/MBC. We present first results of the study. Methods: Pts were age ≥18 yrs with histologically/cytologically confirmed breast adenocarcinoma, measurable LA/MBC, known ER/PgR status, HER2+ disease, and ECOG PS 0–2. No prior chemotherapy was permitted for LA/MBC; prior (neo)adjuvant therapy was allowed. Treatment comprised H (8mg/kg d1 cycle 1→6mg/kg d1) + A (15mg/kg d1) + X (1,000mg/m2 bid d1-14) every 21 days until PD, unmanageable toxicity or consent withdrawal. Primary endpoint: ORR (RECIST). Secondary endpoints: PFS; OS; TTP; safety. Results: From Dec 2008 to Jan 2010, 88 pts, median age 53 yrs (range: 32–82), were enrolled. 22 pts (25%) received (neo)adjuvant H/lapatinib. As of 31 Jul 2010, median follow-up was 8.8 months (range: 0.9–17.1) with 40 pts (46%) still on study. An ORR was seen in 64 pts (72.7%, ITT population), including 6 complete (CR: 6.8%) and 58 partial responses (PR: 65.9%). Taxane-pretreated pts had lower ORR than other subgroups (Table). Median PFS: 14.4 months (95% CI: 10.4–NR); median OS not reached; 12-month survival rate: 95.1%. Treatment-related AEs occurred in 81 pts (92.0%). 19 pts (21.6%) experienced 24 serious AEs, the most common were diarrhea (2.3%) and cardiac failure (2.3%). Hand-foot syndrome (HFS) was the most frequently reported grade 3 treatment-related AE in 22% of pts, but >63% of pts completed >8 cycles of H + A + X therapy. Hematologic AEs and alopecia were rare. 5 pts withdrew due to AEs/intercurrent illness. 84 pts are alive; 1 progressed and died, 3 unrelated deaths were recorded. Conclusions: The combination of H + A + X is clinically active as first-line therapy for HER2+ MBC with a safety profile consistent with prior clinical trials of these agents. Pts, n (%) ORR, % CR, % PR, % ITT population 88 (100) 72.7 6.8 65.9 MBC 74 (84) 73.0 6.8 66.2 LA disease 13 (15) 76.9 7.7 69.2 ER+/PgR+ 37 (42) 70.3 5.4 64.9 ER-/PgR- 51 (58) 74.5 7.8 66.7 Taxane-pretreated 28 (32) 53.6 3.6 50.0 Chemo-naive 37 (42) 78.4 5.4 73.0
The role of PET scan for the detection of incidental gastrointestinal tract lesions in patients examined for lung cancer.
Authors: K. Isobe, Y. Hata, S. Sakaguchi, Y. Takai, S. Sasamoto, K. Shibuya, K. Takagi, S. Homma
Journal: Journal of Clinical Oncology (2010)

e18119 Background: The purpose of this study was to clarify the clinical characteristics of lung cancer patients with the abnormal accumulation in the gastrointestinal tract by fluoro-2-deoxyglucose positron emission tomography (PET). Methods: Of the 968 consecutive patients with primary lung cancer who underwent PET from October 2005 through September 2009, 26 patients had local abnormal accumulation in the gastrointestinal tract. We retrospectively compared the localization of abnormal accumulation in the gastrointestinal tract, standardized uptake value (SUV) max (1 hour), and the final clinical diagnosis. Results: The localization of abnormal accumulation were esophagus in 1, stomach in 8 and small intestine to large intestine in 17, respectively. 14 out of 26 (54%) cases with true PET positive were esophageal cancer in 1, gastric cancer in 2, colon cancer in 8, metastasis to stomach, small intestine and large intestine from lung cancer in one of each. 12 cases with false PET positive were stomach polyp in 1, gastritis in 3, gastrointestinal stromal tumor in 1, colon polyp in 1, diverticulitis in1 and normal physiologic accumulation in 5, respectively. There were no differences in mean SUVmax between malignant lesions, benign lesions, and normal physiologic accumulation. Conclusions: We should perform the endoscopy of digestive tract for the detection of high incidental malignant lesion when the PET showed local abnormal accumulation in the gastrointestinal tract in patients with lung cancer. No significant financial relationships to disclose.
Development and characterization of seed gums from Tamarindus indica and Cassia fistula as disintegrating agent for fast disintegrating Thai cordial tablet
Authors: Kampanart Huanbutta, Wancheng Sittikijyothin
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Crude seed gum and their carboxymethyl derivatives from Tamarindus indica and Cassia fistula seeds were developed and characterized to apply as the pharmaceutical disintegrant in fast disintegrating Thai cordial tablet. The chemical structure of crude gum was chemically modified via carboxymethylation. Degree of substitution (DS) of carboxymethylated gums was determined. Carboxymethylated gums with minimum and maximum DS values were chosen for further application. IR absorption spectra of gum samples were observed to verify their chemical structure changes. In physical properties, the intrinsic viscosity and swelling property of all gum samples were evaluated. The results showed that carboxymethylated gums had higher intrinsic viscosity than those of crude gum. Moreover, they could swell and be soluble in cold water better than those of crude gums. In conclusion, the modified gums from both plants could provide higher hardness and be better used than that crude gums for fast disintegrating Thai cordial tablet. However, this is a preliminary assessment to expressing pharmaceutical application possibility of these gums as disintegrants, diluents and drug release controlling agents.
The Sesquiterpene Lactone Parthenolide Induces Apoptosis and Overcomes the Protective Effect of the Bone Marrow Microenvironment in Human Multiple Myeloma Cells.
Authors: Attaya Suvannasankha, Colin D. Crean, Rajasubramaniam Shanmugam, Rafat Abonour, H. Scott Boswell, Harikrishna Nakshatri
Journal: Blood (2006)
Phase I-II study of DalCM-P [daily dalteparin (Dal), cyclophosphamide (C) and prednisone (P) and bi-weekly methotrexate (M)] as therapy for metastatic breast cancer (MBC)
Authors: R. A. Buckman, N.-S. Wong, M. Clemons, S. Verma, M. E. Trudeau, K. Roche, R. S. Kerbel, G. Deboer, D. J. Sutherland, K. I. Pritchard
Journal: Journal of Clinical Oncology (2005)

695 Background: Preclinical and clinical studies indicate that metronomic chemotherapy (dosing at close, regular intervals with no prolonged breaks) inhibits tumour growth through antiangiogenesis. Metronomic C and M have activity in MBC while Dal (‘Fragmin’) and P have anti-angiogenic activity and are synergistic. We designed a two-stage phase I-II study of DalCM-P in MBC (α=5%, β=10%, Po=5% and P1=20%). Methods: Patients with measurable MBC, adequate end-organ function and performance status, and life expectancy >6 months, who had received ≥2 types of chemotherapy for MBC, or were deemed unsuitable for standard 1st or 2nd line chemotherapy were eligible. Treatment was C 50mg and P 5mg by mouth (po) daily, M 2.5mg po twice daily Mon and Tue, and Dal 5000 IU subcutaneously daily, all given continuously. End points were specified as response rate (RR), time to progression (TTP) and overall survival (OS) using standard RECIST criteria. Results: At interim analysis (Sept 2004), 32 patients were accrued. Characteristics were: median age 56 (range 30–84); hormone receptors positive 22 (68.8%); Her-2 negative 18 (56.3%); visceral disease 24 (75.0%); ≥3 sites of metastases 8 (25.0%); disease free survival >1 year 29 (90.6%). Sixteen (50%) had no prior chemotherapy for MBC; 6 (18.8%) had 1 prior regimen; 10 (31.3%) had ≥2 prior regimens. The only ≥ grade 3 toxicities were transient grade 3 transaminitis in 8 patients (25.0%) and grade 3 vomiting in 1 (3.1%). One patient (3.1%) had complete response (CR), 4 (12.5%) had partial response (PR), 2 (6.3%) had prolonged stable disease ≥ 6 mos (PSD) for an overall response rate (CR+PR+PSD) of 7 (21.9%). Of the 16 with no prior chemotherapy for MBC, 1 had CR, 3 PR and 0 PSD (CR+PR+PSD = 4 (25%)). The median TTP was 1.8 mos (range 0.1–9.1+ mos) and median OS 18.3 mos (range 1.1–18.3+ mos). Data will be available on all 41 patients in May, 2005. Conclusions: DalCM-P is safe, well tolerated and demonstrates clinical activity in MBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Biomira, Ortho-Biotech, Pfizer, Pharmacia, Roche, YM Biosciences AstraZeneca, Aventis, Eli Lilly, Novartis, Pfizer, Pharmacia, Roche, Schering AstraZeneca, Aventis