tbuckley/cabot-search huggingface dataset:
A prospective study examining PROs and other geriatric outcomes in older adults with prostate cancer undergoing chemotherapy.
Authors: Tharsika Manokumar, Salman Aziz, Faraz Rizvi, Henriette Breunis, Anthony Michael Joshua, Ian Tannock, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2013)

9555 Background: Treatment of metastatic castration-resistant prostate cancer (mCRPC) with chemotherapy improves disease control and survival in older men (age 65+) based on large clinical trials. Its effects, though, on more frail elderly men are not well understood and chemotherapy may negatively impact frailty, daily function, physical performance, and quality of life (QOL), particularly outside the clinical trial setting. Methods: Men aged 65+ with mCRPC starting first-line chemotherapy were enrolled in this prospective observational pilot study. Physical function was assessed with the timed up and go (TUG) test, timed chair stands, and grip strength. Frailty was evaluated using the Vulnerable Elders Survey (VES-13) questionnaire in addition to functional status (OARS-IADL), social activities limitations and social support (MOS measures). Patients completed the FACT-P and FACT-G to measure prostate-specific QOL and general QOL, respectively. Assessments were completed before each cycle of chemotherapy. Pre-post within-group comparisons were done using student’s T-tests and linear regression. Results: 25 patients (mean age 75) receiving Docetaxel + Prednisone were enrolled, 3 of whom died and 2 dropped out. Both general and prostate-specific QOL improved over a median of 6 cycles. Patients’ instrumental activities of daily living (IADL) scores remained stable. On average, grip strength was stable and lower extremity function improved on both the TUG and Timed Chair Stands. At baseline, 13 of 25 patients (52%) were frail (VES score 3+). Of the patients that completed chemotherapy, 40% were frail. Conclusions: Contrary to our hypotheses, QOL did not decline in this frail elderly cohort, IADL function remained stable, and physical function remained stable or improved during first-line chemotherapy. Frailty also did not increase at the end of treatment as hypothesized. Older men with mCRPC appear to tolerate first-line chemotherapy fairly well in terms of QOL and geriatric domains.
Effect of three-dimensional collagen I and global histone acetylation on gemcitabine resistance in pancreatic cancer cells.
Authors: Surabhi Dangi-Garimella, Vaibhav Sahai, Mario A. Shields, Hidayatullah G. Munshi
Journal: Journal of Clinical Oncology (2012)

e14515 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. PDAC is also associated with epigenetic changes. We have previously shown that PDAC cells are resistant to gemcitabine in the collagen microenvironment because of increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2) and increased ERK1/2 signaling. Methods: Pancreatic tissue microarrays were stained with trichrome and for histone H3K9, H3K27 acetylation (Ac), and histone acetyltransferase (HATs) expression. PDAC cells were plated onto tissue culture plastic or in 3D collagen gels and protein expression was assessed by Western blotting. DNA damage response was assessed by comet and clonogenic assays. Results: Human PDAC tumors display in areas of fibrosis higher histone H3K9Ac and H3K27Ac. Moreover, PDAC cells upregulate H3K9Ac and H3K27Ac along with GCN5, PCAF and p300 HATs when grown in 3D collagen. Inhibiting ERK1/2 activity and/or decreasing HMGA2 expression attenuates the effect of collagen on H3Ac and HAT expression. Human PDAC tumors with HMGA2 also demonstrate H3Ac and HAT expression. Additionally, cells in 3D collagen demonstrate reduced tailing with the comet assay, increased clonogenic potential and increased γH2AX following gemcitabine treatment, suggesting an increased repair response to damaged DNA in the collagen microenvironment. Significantly, downregulation of HATs along with inhibition of ERK1/2 activity attenuates gemcitabine-induced γH2AX detected in 3D collagen. Conclusions: Collagen microenvironment limits the effectiveness of gemcitabine through ERK1/2 and HMGA2-dependent HAT expression. HMGA2 expression is associated with histone acetylation and HAT expression in human PDAC tumors, particularly in area of fibrosis, suggesting that fibrosis may contribute to chemo-resistance through increased HMGA2-HAT signaling. Given that very little progress has been made in the treatment of pancreatic cancer, targeting HATs could be a novel approach to sensitize pancreatic tumors to chemotherapy.
Tandem activated photodynamic and chemotherapy: Using pH-Sensitive nanosystems to realize different tumour distributions of photosensitizer/prodrug for amplified combination therapy
Authors: Yu Ji, Feng Lu, Wenbo Hu, Hui Zhao, Yufu Tang, Bing Li, Xiaoming Hu, Xiang Li, Xiaomei Lu, Quli Fan, Wei Huang
Journal: Biomaterials (2019)
A Phase II Multicenter Single Arm Study of Ibrutinib in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma
Authors: Radhakrishnan Ramchandren, Tycel J. Phillips, Sumana Devata, Ali M. Gabali, Christiane Houde, Silva Pregja, Golbon Aghamohammadi, Emily Wesson, Tony Hutto, Michelle A. Fanale
Journal: Blood (2017)
光化性角化病日光光动力疗法:对比 BF‐200 ALA 与 MAL 的多中心试验
Authors: J.E. Räsänen, N. Neittaanmäki, L. Ylitalo, J. Hagman, P. Rissanen, L. Ylianttila, M. Salmivuori, E. Snellman, M. Grönroos
Journal: British Journal of Dermatology (2019)

光化性角化病(AK)是被阳光晒伤的皮肤区域,多见于受到阳光暴晒的身体部位。起初很难看到病灶,但能够感觉到皮肤变硬,就像砂纸一样。病灶直径可能增至1~2厘米。高达20%的AK可能会在10~25年内发展成一种名为鳞状细胞癌(SCC)的皮肤癌。该病症的一种治疗方法为日光光动力疗法(DL‐PDT),需要在病灶(受影响的皮肤区域)上涂敷含有“感光剂”的乳膏。感光剂本身是非活性的。但是当特定波长的光线照射在涂有感光剂的皮肤上时,感光剂会被激活,这种治疗可杀灭皮肤中的异常细胞。本研究的目的在于对比两种感光剂BF‐200 ALA与MAL的疗效(药物的功效)、耐受性(包括疼痛和副作用)及成本效益。总共69名患者(合计767个AK病灶对称分布在脸部或头皮)在芬兰的三个中心接受治疗。以随机脸部分开的设计形式(即,一半脸用一种感光剂治疗,另一半脸用另一种治疗)进行一段时间的DL‐PDT治疗。设盲观察者在治疗后12个月评估结果,他们不知道每侧脸采用哪种治疗。作者发现,BF‐200 ALA清除的AK病灶数显著多于MAL (79.7% vs 73.5%)。在对比同一患者的两半脸时,BF‐200 ALA治疗侧的AK清除率显著优于MAL治疗侧。接受两种感光剂治疗的患者在光治疗过程中报告的疼痛都很少,两者之间无显著差异。在DL‐PDT治疗后一周与治疗相关的皮肤反应在BF‐200 ALA治疗侧更强烈。在使用两种感光剂治疗的>90%病例中12个月的美容效果(外观效果)极好或很好。两种感光剂的DL‐PDT治疗成本类似,但BF‐200 ALA的疗效稍高。作者的结论是,在轻度和中度AK的DL‐PDT治疗中,BF‐200 ALA较MAL更有效,且性价比略胜一筹。
An artificial intelligence-enabled ECG algorithm for the identification of patients with atrial fibrillation during sinus rhythm: a retrospective analysis of outcome prediction
Authors: Zachi I Attia, Peter A Noseworthy, Francisco Lopez-Jimenez, Samuel J Asirvatham, Abhishek J Deshmukh, Bernard J Gersh, Rickey E Carter, Xiaoxi Yao, Alejandro A Rabinstein, Brad J Erickson, Suraj Kapa, Paul A Friedman
Journal: The Lancet (2019)
Long term follow up after treatment of hairy cell leukemia with 2-CdA
Authors: M. Ramzi, M. Haghshenas
Journal: Journal of Clinical Oncology (2006)

16518 Background: Hairy cell leukemia (HCL) is a chronic B cell disorder that follows an indolent but progressive course. The ability of new purine analogue deoxyadenosine to induce long lasting complete remission in patients with hairy cell leukemia has revolutionized the treatment of this disease. We report the long term outcomes of patients with HCL treated in Shiraz, in south of Iran,with this drug. Methods: Between October 1993 till April 2004, 79 patients with classic symptomatic hairy cell leukemia were treated with 2-cholorodeoxy adenosine (2-CdA) with dose of 0.1 mg/kg of body weight per day by continuous intravenous infusion for 7 days. Results: sixty nine (87%) of patients achieved an initial complete response and 10 (12.6) a partial response with an overall median duration of response follow up of 78 months. Five patients had relapsed at a median of 43 months. All of 5 patients after relapse treated with second courses of 2-CdA, 4 (80%) achieved second complete responses and one (20%) partial response. In our study we had not any case of second malignancy after treatment with 2-CdA with median follow up of 82.5 months. Conclusion: This study confirms single course of 2-CdA induced long lasting complete response in the vast majority of patients. Relapse rate for complete responders were low. Patients who relapse can be successfully retreated with this drug, so we conclude 2-CdA had high efficacy and a favorable acute and long term toxicity profile in our patients in south of Iran, without any increase in risk of second malignancy. No significant financial relationships to disclose.
Decoupling the mechanism of action of efrapeptins, dual inhibitors of proteasome and Hsp90 chaperone function: The possible role of endoplasmic reticulum stress
Authors: Adonia Papathanassiu
Journal: Cancer Research (2008)

LB-184  Efrapeptins is a family of small, naturally occurring oligopeptides with potent antitumor activity in vitro and in vivo. Although efrapeptins are known for their ability to inhibit F1F0-ATPase, the enzyme responsible for the mitochondrial production of ATP, their antitumor actions have been attributed to their ability to inhibit the chymotrypsin-like and caspase-like activities of 26S proteasome and to suppress Hsp90 chaperone function by dissociating the complex of Hsp90 with its co-chaperone F1F0-ATPase. Breast cancer cells are particularly sensitive to the inhibitory activities of efrapeptins (IC50 values range between 5 and 100 nM) with the exception of the MDA-MB-231 cell line (IC50 ~4,000 nM). Here, the mechanisms determining cell sensitivity to the antitumor activities of efrapeptins are explored. As detected by Western immunoblotting, accumulation of ubiquitinated proteins after a brief treatment of MDA-MB-231 cells with efrapeptins suggests proteasomal inhibition. Interestingly, no appreciable accumulation of ubiquitinated proteins is observed in the efrapeptin-sensitive MCF-7 cells. Efrapeptin-induced dissociation of the Hsp90:F1F0-ATPase complex is detected in both cell lines indicating the presence of a functional F1F0-ATPase. However, accumulation and not degradation of mutated p53 after overnight treatment of MDA-MB-231 cells with efrapeptins indicates that Hsp90 client proteins in MDA-MB-231 cells may not be affected by the dissociation of the Hsp90:F1F0-ATPase complex as do in MCF-7 cells. Examination of the protein levels of Hsp90 and F1F0-ATPase reveal that MCF-7 cells possess 2.2-fold more Hsp90 and 8-fold more F1F0-ATPase than MDA-MB-231 cells, which may explain why inhibition of proteasome is the predominant mechanism of action in MDA-MB-231 cells. The reduction in the levels of F1F0-ATPase in the MDA-MB-231 cell line is in agreement with the dependence of the cells on glycolysis for ATP synthesis. Consequently, MDA-MB-231 cells possess increased levels of glucose regulated proteins, i.e., 3.2-fold more Grp78 and 1.5-fold more Grp94 than MCF-7 cells and express the glucose transporter Glut-1 while MCF-7 cells do not. Efrapeptin-treatment results in upregulation of Grp94 (both cell lines) and Grp78 (MDA-MB-231 only) without evidence of a concomitant endoplasmic reticulum (ER) stress induction. On the contrary, efrapeptin-treatment leads to downregulation of P-PERK, a known ER stress sensor. Downregulation of P-PERK has been associated with decreased resistance to ER stress suggesting that efrapeptin treatment may render tumor cells vulnerable to environmental conditions that promote ER-stress such as hypoxia and lack of nutrients. This may further explain the antitumor activity of efrapeptins.
Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 36-month results.
Authors: Shunji Takahashi, Takuji Iwase, Norio Kohno, Takashi Ishikawa, Seung Jin Kim, Mitsuchika Hosoda, Jun Horiguchi, Hideko Yamauchi, Yasuo Hozumi, Morihito Okada, Masao Fukunaga, Shinzaburo Noguchi
Journal: Journal of Clinical Oncology (2013)

e20510 Background: We reported 12-month results of upfront zoledronic acid (ZOL) therapy, which prevented bone loss in postmenopausal Japanese women who were receiving adjuvant letrozole, confirming the Z-FAST and ZO-FAST studies results. But the examination in the long term of aromatase inhibitor-associated bone loss has not been proved in the Japanese or Asia women. Methods: Postmenopausal women with hormone receptor positive early breast cancer (BC) patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start ZOL (4mg intravenously every 6 months) for 5 years. The delayed group received ZOL when lumbar spine (L 2 -L 4 ) BMD decreased to less than young adult mean (YAM) – 2.0 S.D or when a nontraumatic fractured occurred. The primary endpoint of this study was to compare the changes in L 1 -L 4 BMD at month 12 between the groups. Secondary endpoints, measured at other predetermined timepoints, included comparing changes in L 1 -L 4 , L 2 -L 4 and total hip (TH) BMD and markers of bone turnover, fracture incidence, and time to disease recurrence. We report the results of 36-month interim analysis. Results: At 36 months, mean change in L 1 -L 4 BMD was 10.7% higher in the upfront group than in the delayed group ( 95% CI, 9.2% to 12.1%; p&lt; 0.001 ), L 2 -L 4 BMD was 10.9% higher ( 95% CI, 9.3% to 12.5%; p&lt; 0.001 ), and TH BMD was 6.7% higher ( 95% CI, 5.3% to 8.1%; p&lt; 0.001 ). The incidence of fracture was not significantly different between each group (upfront, 1(1.0%) vs. delayed, 4(4.1%)). Disease recurrence was reported in 3 upfront (3.1%) and 1 delayed (1.0%) patients. By month 36, 11 patients (11.3%) in the delayed group initiated ZOL therapy. There was no significant difference of adverse events other than fever with ZOL at the first treatment between the two groups. Conclusions: Upfront ZOL seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal Japanese women with early BC who were receiving adjuvant letrozole for 36 months. Clinical trial information: UMIN000001104.
A phase Ib study of the combination of temsirolimus (T) and pegylated liposomal doxorubicin (PLD) in advanced or recurrent breast, endometrial, and ovarian cancer.
Authors: Marye Boers-Sonderen, Ingrid Desar, Winette T.A. Van Der Graaf, P. B. Ottevanger, Carla Van Herpen
Journal: Journal of Clinical Oncology (2012)

5061 Background: PLD is active in metastatic breast, endometrial and ovarian cancer. Preclinical studies suggest that mTOR inhibitors (mTORi), such as T, have an additive therapeutic effect to chemotherapy and resistance to doxorubicin can be reversed by adding an mTORi. Therefore, the combination of T and PLD is highly promising. Methods: This phase I study assessed the maximum tolerated dose (MTD), safety and activity of the combination of T and PLD in advanced or recurrent breast, endometrial or ovarian cancer. Patients (pts) who were not previously treated with PLD or T, with adequate organ function were eligible. After a two week run in period with T iv once weekly, PLD iv once every four weeks was added. In case of clinical benefit, pts were treated for a maximum of 9 cycles combination therapy. T could be continued as monotherapy afterwards. The MTD was defined as the highest dose at which ≤ 1 dose limiting toxicity (DLT) had been observed among 6 pts. FDG PET scans were performed at baseline and after 2 and 6 wks to assess the effect on tumor metabolism. Pharmacokinetic (PK) sampling was performed during cycle 1. Results: 20 pts were enrolled. On the 4th dose level with 20 mg T and 40 mg/m 2 PLD 2 DLTs occurred in 6 pts: a grade 3 thrombocytopenic bleeding and a grade 3 skin toxicity. Therefore, the MTD was assessed at 15 mg T and 40 mg/m 2 PLD. Adverse events (all grades/grade 3-4 in %) occurring most frequently were fatigue (84/5), nausea (84/16), mucositis (79/21), vomiting (74/16) and anorexia (74/0) Furthermore, rash and hand foot syndrome occurred both in 53% of pts, with 11% and 21% grade 3 respectively. 3 pts had a confirmed PR and 9 had SD (&gt; 3 months). The mean progression free survival (PFS) was 4.9 months with 2 pts still on treatment. Results of FDG PET and PK data are currently being analyzed and will be presented. Conclusions: The combination of T and PLD is safe and tolerable. The MTD was assessed at PLD 40 mg/m 2 once every 4 weeks and T 15 mg weekly. The activity of this combination in breast, endometrial and ovarian cancer pts is promising and warrants further studies.
Does biomarker information impact patients’ preferences for therapy?
Authors: Ann H. Partridge, Karen Sepucha, Anne O'Neill, Kathy Miller, Emily Baker, Chau T. Dang, Donald W. Northfelt, George W. Sledge, Bryan P. Schneider
Journal: Journal of Clinical Oncology (2013)

6527 Background: Biomarker information can risk stratify patients based on potential for benefits/toxicity from therapy. Ideally, a biomarker will identify those who benefit with limited toxicity. However, the impact of biomarkers is unclear when indicting individuals with greatest benefit are also at increased risk for toxicity. Methods: We surveyed participants at 18 month follow-up in the Decision-Making/Quality of Life (DM-QOL) component of ECOG5103, a RCT where patients were randomized to receive adjuvant chemotherapy for breast cancer with either placebo or bevacizumab (in 2 schedules). We asked patients for the preferred treatment in two hypothetical scenarios: 1) preference for chemo A or chemo A + B without biomarker information; 2) preference for chemo A or chemo A+B when participants tested positive for a “B-receptor” which increased both the benefit and toxicity of chemo A+B. McNemar’s test was used to examine changes in preferences. Results: 439 patients completed both scenarios on 18-month survey. The Table shows the treatment preferences in each scenario. The positive biomarker information in scenario 2 led 60/439 (14%) participants to switch their preference. The main reason for treatment preference in scenario 2 was greater benefits of chemo A+B (64%), the lower risks with chemo A (20%) and positive biomarker (10%). Among participants who changed preference, those randomized to receive bevacizumab were more likely to switch to chemo A in scenario 2. Conclusions: Information about a positive biomarker, indicating increased benefit and increased risk from additional chemo, did not significantly change participants’ preferred treatment. All participants were involved in a large placebo controlled double blind trial and the majority (70%) preferred the most aggressive course of treatment in both scenarios. Whether patients not enrolled in the trial would be more sensitive to the increased risk information is unclear. [Table: see text]
Is there a CA-125 level that predicts negative second look surgery (SLS) in patients with advanced epithelail ovarian cancer (EOC)?
Authors: S. Sharma, P. Singhal, K. Odunsi, S. Lele
Journal: Journal of Clinical Oncology (2006)

15042 Background: The value of second look surgery (SLS) in advanced epithelial ovarian cancer (EOC) has been has been questioned because performing this procedure has not been associated with a clear survival advantage.However, SLS continues to be the most accurate means of documenting the response to chemotherapy, and therfore still used in investigational protocols. The primary purpose of this study was to assess the levels of CA 125 after treatment, that could predict absence of disease at SLS. Methods: Between 1998 and 2003, 98 stage III EOC patients who underwent optimal cytoreductive surgery, completed 6 cycles of platinum/paclitaxel chemotherapy, and were NED (no evidence of disease: normal CA 125, normal physical and radiological examination) were included in this study. SLS was performed at 6–8 weeks from completion of primary therapy. Patients with disease present at SLS were considered to have persistent disease and received second line chemotherapy. Patient demographics, surgical and chemotherapy treatments, and CA 125 levels prior to start and at completion of primary treatment were collected retrospectively. Survival was estimated by the Kaplan-Meier method. Results: Forty seven out of 98 (48%) of optimally debulked patients who were NED at completion of primary therapy underwent SLS. Twenty-five out of 47 patients (53%) had evidence of disease at SLS and 22 out of 47 patients (47%) were NED at SLS. The median disease free survival was 42 months (95% CI 16, 81) in patients with negative SLS compared with 17 months (95% CI 9, 45) in patients who did not undergo SLS (p = 0.03). Estimated 5-year survival in patients with negative SLS was 90% compared to 50% in patients who did not undergo SLS (p = 0.05). CA 125 levels of ≤ 10 after completion of primary therapy was predictive of negative SLS (p &lt; 0.05). Conclusions: SLS evaluation of disease status appears to be a more accurate than standard clinical evaluation in patients who are NED at completion of their primary therapy. Negative SLS also appears to be a predictor of improved disease free and overall survival. Furthermore, CA 125 ≤ 10 is predictive of negative SLS in patients who are NED after completion of primary therapy. No significant financial relationships to disclose.
Phase II study of docetaxel and S-1 combination therapy in patients with previously treated non-small cell lung cancer
Authors: S. Atagi, M. Kawahara, A. Kubo, T. Kawaguchi, K. Yumine, K. Okishio, Y. Tomizawa, H. Komatsu, S. Fukai
Journal: Journal of Clinical Oncology (2007)

18122 Background: Docetaxel is active against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). S-1 is a novel oral fluoropyrimidine, composed of tegafur, 5-chloro-2,4-dihydroxypyridine (dihydropyrimidinedehydrogenase inhibitor), and potassium oxonate (orotate phosphoribosyl transferase inhibitor). It has been commercially available and used for NSCLC in Japan. We conducted this study to evaluate the efficacy and safety of docetaxel combined with S-1 in NSCLC patients (pts) who were previously treated with one or more regimens. Methods: Eligible pts were required to have histologically or cytologically confirmed measurable or evaluable stage IIIB or IV NSCLC, age= 20 years, one or more previous chemotherapy, a performance status (PS) 0–1, and adequate organ function and bone marrow reserve. In this study, pts received S-1 (80 mg/m 2 orally on days 1–14) and docetaxel (40mg/m2 IV on days 1). Treatment was repeated every 3 weeks. Results: Between January 2005 and May 2006, 30 pts were enrolled on this study. 29 pts were eligible and evaluable. Median age was 67 (48–79), male/female (23/6), PS 0/1 (9/20), stage IIIB/IV (7/22), and prior chemotherapy regimen 1/2/3 (23/4/2). 28 pts received a platinum-based chemotherapy. Response: PR=7(24%), SD=13, PD=7, NE=2. Median survival time was 10.2 months. Grade 3/4 toxicities (% of pts) were as follows: leukocytes 6/0 (20.6%), neutrophils 7/3 (34.4%), platelets 0/0, infection 0/1 (3.4%), fever 2/0 (6.9%), diarrhea 1/0 (3.4%), neurology 0/1 (3.4%), and mucositis 1/0 (3.4%). There were no treatment-related deaths. Conclusions: The combination of docetaxel and S-1 was effective with acceptable toxicity in pts with previously treated NSCLC. These results warrant further investigations of this regimen a randomized controlled trial as a second-line treatment for NSCLC. No significant financial relationships to disclose.
Abstract 12364: Addressing Outcome Prediction in Heart Failure Using Contemporary Equations for Maximal Oxygen Consumption
Authors: Kegan J Moneghetti, Jeffrey W Christle, Julia Hock, Ross Arena, Leonard A Kaminsky, Matthew Wheeler, Francois Haddad, Euan Ashley, Jonathan Myers
Journal: Circulation (2017)

Background: Peak oxygen consumption (VO2) has been well validated in risk of all-cause mortality and as a prognostic marker in heart failure (HF). Despite VO2 being considered a standard measure du...