tbuckley/cabot-search huggingface dataset:
Cancer Mortality Among Recipients of Solid-Organ Transplantation in Ontario, Canada
Authors: Sergio A. Acuna, Kimberly A. Fernandes, Corinne Daly, Lisa K. Hicks, Rinku Sutradhar, S. Joseph Kim, Nancy N. Baxter
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Solid-organ transplant recipients (SOTRs) are at greater risk of developing some cancers than the general population; however, because they are also at increased risk of mortality from noncancer causes, the effect of transplantation on cancer mortality is unclear. <h3>Objective</h3> To describe cancer mortality in SOTRs and to assess whether SOTRs are at increased risk of cancer mortality compared with the general population. <h3>Design, Setting, and Participants</h3> Population-based cohort study of patients who underwent solid-organ transplantation in Ontario, Canada, between 1991 and 2010 with 85 557 person-years of follow-up through December 31, 2011. Solid-organ transplantation was identified using the national transplant register and linked to the provincial cancer registry and administrative databases. The analysis was conducted between November 2013 and February 2015. <h3>Exposure</h3> Solid-organ transplantation. <h3>Main Outcomes and Measures</h3> Cancer mortality for SOTRs was compared with that of the general population using standardized mortality ratios (SMRs). Mortality and cause of death were ascertained by record linkage between the Canadian Organ Replacement Register, the Ontario Cancer Registry, and the Office of the Registrar General of Ontario death database. <h3>Results</h3> A total of 11 061 SOTRs were identified, including 6516 kidney, 2606 liver, 929 heart, and 705 lung transplantations. Recipients had a median (interquartile range) age of 49 (37-58) years, and 4004 (36.2%) were women. Of 3068 deaths, 603 (20%) were cancer related. Cancer mortality in SOTRs was significantly elevated compared with the Ontario population (SMR, 2.84 [95% CI, 2.61-3.07]). The risk remained elevated when patients with pretransplant malignant neoplasms (n = 1124) were excluded (SMR, 1.93 [95% CI, 1.75-2.13]). The increased risk was observed irrespective of transplanted organ. The SMR for cancer death after solid-organ transplantation was higher in children (SMR, 84.61 [95% CI, 52.00-128.40]) and lower in patients older than 60 years (SMR, 1.88 [95% CI, 1.62-2.18]) but remained elevated compared with the general population at all ages. <h3>Conclusions and Relevance</h3> Cancer death rate in SOTRs was increased compared with that expected in the general population; cancer was the second leading cause of death in these patients. Advances in prevention, clinical surveillance, and cancer treatment modalities for SOTRs are needed to reduce the burden of cancer mortality in this population.
Redirecting Transport of Nanoparticle Albumin-Bound Paclitaxel to Macrophages Enhances Therapeutic Efficacy against Liver Metastases
Authors: Tomonori Tanei, Fransisca Leonard, Xuewu Liu, Jenolyn F. Alexander, Yuki Saito, Mauro Ferrari, Biana Godin, Kenji Yokoi
Journal: Cancer Research (2016)

Current treatments for liver metastases arising from primary breast and lung cancers are minimally effective. One reason for this unfavorable outcome is that liver metastases are poorly vascularized, limiting the ability to deliver therapeutics from the systemic circulation to lesions. Seeking to enhance transport of agents into the tumor microenvironment, we designed a system in which nanoparticle albumin-bound paclitaxel (nAb-PTX) is loaded into a nanoporous solid multistage nanovector (MSV) to enable the passage of the drug through the tumor vessel wall and enhance its interaction with liver macrophages. MSV enablement increased nAb-PTX efficacy and survival in mouse models of breast and lung liver metastasis. MSV-nAb-PTX also augmented the accumulation of paclitaxel and MSV in the liver, specifically in macrophages, whereas paclitaxel levels in the blood were unchanged after administering MSV-nAb-PTX or nAb-PTX. In vitro studies demonstrated that macrophages treated with MSV-nAb-PTX remained viable and were able to internalize, retain, and release significantly higher quantities of paclitaxel compared with treatment with nAb-PTX. The cytotoxic potency of the released paclitaxel was also confirmed in tumor cells cultured with the supernatants of macrophage treated with MSV-nAB-PTX. Collectively, our findings showed how redirecting nAb-PTX to liver macrophages within the tumor microenvironment can elicit a greater therapeutic response in patients with metastatic liver cancer, without increasing systemic side effects.
P0092 : IL-17 A and F isoforms and their receptors mediate liver damage in experimental cholestasis and the IL17 A/F heterodimer induces a profibrogenic profile in hepatic stellate cells in vitro
Authors: S. Zepeda-Morales, S. Del Toro-Arreola, L Sánchez-Orozco, M. Fafutis-Morris, L. García-Benavides, A.L Pereira-Suárez, M.R. Bueno-Topete
Journal: Journal of Hepatology (2015)
Impact of pegylated liposomal doxorubicin (PLD) plus docetaxel (D) versus single-agent D on health-related quality of life (HRQOL) of patients with advanced breast cancer (BC) previously treated with neoadjuvant-adjuvant anthracycline
Authors: S. A. Tjulandin, I. N. Bondarenko, V. F. Semiglazov, O. I. Balashova, A. N. Makhson, N. V. Bogdanova, Y. Wu, V. A. Chatikhine, Z. Yuan, J. A. Sparano
Journal: Journal of Clinical Oncology (2009)

e20522 Background: A randomized, multicenter phase 3 trial of PLD+D showed a significant improvement in the primary endpoint of time to progression (TTP) compared with D alone but with increased Grade 3/4 hand-foot syndrome (HFS: 24% vs. 0%) and mucositis/stomatitis (M/S: 12% vs. 1%) in patients (pts) with advanced breast cancer (BC). (Sparano JA et al. SABCS 2008. #80) This analysis evaluated HRQOL in these pts. Methods: Pts were randomized to D 75 mg/m 2 (N=373) or PLD 30 mg/m 2 + D 60 mg/m 2 (N=378) on Day 1 every 21 days until progression or unacceptable toxicity. HRQOL was assessed using the Functional Assessment of Cancer Therapy - Breast (FACT-B) at baseline and at every cycle during treatment. FACT-B has 4 primary domains: physical, social/family, emotional, and functional, plus a BC-specific subscale. The primary analysis was a t-test comparison of change in the trial outcome index (TOI) from baseline to the last evaluation. TOI combined physical/functional domain scores with BC-specific scores. Other FACT-B endpoints analyzed included FACT-B total score and individual subscales. Also, % pts meeting an established minimally important difference (MID) of HRQOL improvement in TOI was assessed. Results: Median number of cycles was 6 for both arms. TOI was available for 97.9% of all scheduled assessments for both treatment groups. At baseline, mean FACT-B and TOI scores were similar for PLD+D vs D arms (94.2±18.6 vs 95.3±18.7 and 59.7±13.8 vs 60.2±13.4, respectively); other FACT-B domains were also similar. PLD+D vs D arms showed similar mean change from baseline to last evaluation in TOI (-4.6±12.2 vs -6.0±12.4; P=0.13). Other FACT-B subscales showed 1–2 point differences across domains over time. Likewise, % pts reaching MID was similar across arms. Pts in both arms experienced similar FACT-B declines as disease progressed. Conclusions: Despite increased HFS and M/S with PLD+D vs D alone, HRQOL was comparable for both arms. [Table: see text]
肥大型心筋症患者における 99m Tc-テトラフォスミン心筋SPECTにより評価した、ナトリウム利尿ペプチド血しょう中濃度と冠血流リザーブとの関係性
Authors: Zen K, Hikosaka T, Sakamoto K, Yamano T, Irie H, Takamiya M, Nakagawa M, Nakamura T, Nishimura T
Journal: Circulation (2002)
Pharmacoepidemiology of clinically relevant hypothyroidism and hypertension from sunitinib and sorafenib.
Authors: C. M. Walko, R. E. Aubert, N. M. La-Beck, G. Hawk, V. Herrera, H. Kourlas, R. S. Epstein, H. L. McLeod
Journal: Journal of Clinical Oncology (2010)

9149 Background: Sunitinib (SUN) and sorafenib (SOR) are oral tyrosine kinase inhibitors approved for renal cell carcinoma and gastrointestinal stromal tumors (SUN) and hepatocellular carcinoma (SOR). Sporadic reports of thyroid dysfunction and hypertension (HTN) have been made with these agents. Determination of the true side effect incidence will allow for more efficient monitoring and treatment recommendations. Methods: An observational cohort study was performed using de-identified pharmacy claims data from 2006 to 2009 to evaluate patients (pts) who were prescribed SUN, SOR or capecitabine (CAP). The primary outcome was time to first prescription for thyroid replacement (TR) or HTN treatment. CAP was used as a comparison group for drug-induced hypothyroidism or HTN. Pts were included if they had at least 2 consecutive prescriptions or 45 days of consecutive therapy. Exclusion criteria included presence of concurrent prescriptions for other oral cancer therapies or active prescriptions for TR or HTN therapy. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated by cox proportional hazards models adjusted for age, sex and chronic disease score. Results: A total of 20,061 pts were eligible for evaluation of TR therapy, 1,965 receiving SUN, 1,790 SOR and 16,306 CAP. TR therapy was initiated in 11.6% of those receiving SUN (HR 16.77, CI 13.54, 20.76), 2.6% SOR (HR 3.47, CI 2.46, 4.98) and 1% CAP The median time for needing TR therapy was 4 months. A total of 14,468 pts were eligible for evaluation of HTN therapy, 1,207 SUN, 1,102 SOR, and 12,159 CAP. HTN therapy was initiated in 21% of those receiving SUN (HR 4.91 CI 4.19, 5.74), 14% SOR (HR 3.25, CI 2.69, 3.91), and 5% capecitabine. The median time for needing HTN therapy was 2 months. Conclusions: Pts receiving SUN and SOR have a similar, but elevated, risk of clinically relevant HTN. Clinically relevant hypothyroidism is more than 4 times more common with SUN than SOR. Clinically relevant hypothyroidism usually occurs between 1 and 7 months after the initiation of SUN or SOR therapy. This data provides robust measures of the incidence of these clinically actionable adverse events and implies mechanistic distinctions between the two agents. No significant financial relationships to disclose.
The number of residual metastatic lymph nodes following neoadjuvant chemotherapy predicts disease-free survival in patients with stage III NSCLC
Authors: S. Kim, B. Cho, J. Moon, H. Choi, S. Shin, J. Sohn, J. Kim
Journal: Journal of Clinical Oncology (2007)

18024 Background: The prognosis of patients with stage III non-small cell lung cancer (NSCLC) who achieved pathological complete response or downstaging following neoadjuvant chemotherapy is better than those with residual metastatic lymph node (LN). However, the prognostic significance of the number of residual metastatic LNs remains unclear. Methods: From January 2001 to January 2006, 42 consecutive patients with stage IIIAN2 (22 patients) and IIIB without pleural effusion (20 patients) were treated with neoadjuvant chemotherapy. Thirty four of 42 patients were pathologically staged by mediastinoscopy. Neoadjuvant chemotherapy consisted of 3 cycles of platinum based doublet (21 patients with gemcitabine, 15 with paclitaxel, and 6 with docetaxel). Results: After neoadjuvant chemotherapy, pathological complete response and downstaging was achieved in one patient and 24 patients, respectively. No pathological LN metastasis was present in 9 patients (21.4%), and LN metastasis was present in 33 patients (78.6%). With a median follow up of 23 months, the 2-year disease free survival (DFS) rate of patients without residual LN metastasis was statistically better than that of patients with residual LN metastasis (46% and 18% in patients with residual LN, p=0.03). Among 33 patients with residual LN metastasis, age (p=0.01), pathological downstaging (p=0.09) and number of residual metastatic LNs (median 14 months in LN =4 vs median 5 months in LN =5; p=0.01) were significant predictors of DFS in univariate analysis. In multivariate analysis, number of residual metastatic LNs was an independent predictor of DFS among patients with residual LN metastasis, irrespective of pathological downstaging. Conclusions: The number of residual metastatic lymph nodes following neoadjuvant chemotharpy is an independent predictor of DFS in patients with stage III NSCLC. No significant financial relationships to disclose.
p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients.
Authors: R Silvestrini, E Benini, S Veneroni, M G Daidone, G Tomasic, P Squicciarini, B Salvadori
Journal: Journal of Clinical Oncology (1996)

BACKGROUND AND PURPOSE The tumor-suppressor gene TP53 and the proto-oncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and for a mitochondrial protein involved in multiple cellular functions. The proteins provide prognostic information in node-negative breast cancer and are supposed to influence treatment responsiveness. We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year. PATIENTS AND METHODS On 240 resectable cancers, we determined the expression of p53 and bcl-2, using immunohistochemistry, cell proliferation (3H-thymidine labeling index [3H-dT LI]), and ER and progesterone receptors (PgR). RESULTS p53 expression and 3H-dT LI were weakly related to one another and both were unrelated to bcl-2. Relapse-free and distant metastasis-free survival at 5 years were significantly lower for patients with tumors that highly expressed p53 (P = .0001) and for those that weakly expressed or did not express bcl-2 (P = .02). However, p53, but not bcl-2, provided prognostic information independent of tumor size, axillary node involvement, steroid receptors, and 3H-dT LI. Moreover, the simultaneous p53 overexpression and lack of PgR identified patients at maximum risk of relapse, whereas bcl-2 overexpression, associated with a low 3H-dT LI or the presence of PgR, improved the prognostic resolution for low-risk patients. CONCLUSION p53 expression appears to be indicative of clinical outcome in postmenopausal patients treated with tamoxifen. Whether p53 overexpression and weak bcl-2 expression are indicators of biologic aggressiveness, regardless of treatment, or of hormone resistance remains to be defined.
Rare A2ML1 variants confer susceptibility to otitis media
Authors: Regie Lyn P Santos-Cortez, Charlotte M Chiong, Ma Rina T Reyes-Quintos, Ma Leah C Tantoco, Xin Wang, Anushree Acharya, Izoduwa Abbe, Arnaud P Giese, Joshua D Smith, E Kaitlynn Allen, Biao Li, Eva Maria Cutiongco-de la Paz, Marieflor Cristy Garcia, Erasmo Gonzalo D V Llanes, Patrick John Labra, Teresa Luisa I Gloria-Cruz, Abner L Chan, Gao T Wang, Kathleen A Daly, Jay Shendure, Michael J Bamshad, Deborah A Nickerson, Janak A Patel, Saima Riazuddin, Michele M Sale, Tasnee Chonmaitree, Zubair M Ahmed, Generoso T Abes, Suzanne M Leal
Journal: Nature Genetics (2015)
Prostate cancer treatment and risk of acute myeloid leukemia in a population-based prospective cohort
Authors: R. P. Ojha, R. Thertulien, Y. Zhou, L. A. Fischbach
Journal: Journal of Clinical Oncology (2008)

5073 Background: Limited information is available regarding the risk of acute myeloid leukemia (AML) for prostate cancer patients treated with radiation. We conducted a prospective cohort study to determine whether prostate cancer patients treated with external beam radiation therapy (EBRT), surgery, or combination therapy (EBRT and surgery) have a greater risk of developing AML than untreated patients. Methods: We utilized Surveillance, Epidemiology, and End Results 9 (SEER 9), a population-based cancer registry representative of the United States, to establish a prospective cohort for whom complete treatment and AML incidence data were available. The cohort (n=177,386) was restricted to men with newly diagnosed primary prostate cancer from January 1988-December 2003 who did not develop secondary cancers other than AML. Cox proportional hazards regression was used to estimate the relative risk (RR) of AML incidence. Results: The cohort yielded 248 AML cases (incidence density = 23/100,000 person-years). Prostate cancer patients treated with EBRT, surgery, or combination therapy had a greater risk of developing AML than untreated patients after controlling for age, race, grade, and stage of prostate cancer. However, patients who received EBRT had consistently greater risk of developing AML across 5-year intervals than patients who underwent surgery (EBRT: 5-yr RR=2.47, 95% CI=1.51, 4.06; 10-yr RR=2.20, 95% CI=1.46, 3.30; 15-yr RR=1.97, 95% CI=1.32, 2.94. Surgery: 5-yr RR=1.52, 95% CI=0.92, 2.50; 10-yr RR=1.50, 95% CI=1.00, 2.25; 15-yr RR=1.19, 95% CI=0.80, 1.79). Patients who received combination therapy had risk estimates similar to EBRT alone (5-yr RR=2.99, 95% CI=1.52, 5.88; 10-yr RR=2.82, 95% CI=1.67, 4.77; 15-yr RR=2.08, 95% CI=1.25, 3.44). Conclusions: Our data indicate that prostate cancer patients who receive EBRT have almost a 2-fold greater risk of developing AML 15-years after prostate cancer diagnosis than patients who undergo surgery. Furthermore, AML risk plateaus 5 years after prostate cancer diagnosis for patients who receive EBRT. Our findings should be considered in the full context of potential risks and benefits associated with primary treatment of localized prostate cancer. No significant financial relationships to disclose.
Identification of a novel kinase over-expressing in hormone refractory prostate cancer and its possibility as a therapeutic target for prostate cancer
Authors: Su-Youn Chung, Hidewaki Nakagawa, Kenji Tamura, Mutsuo Furihata, Motohide Uemura, Toyomasa Katagiri, Yasutomo Nasu, Hiromi Kumon, Tsuneharu Miki, Taro Shuin, Tomoaki Fujioka, Yusuke Nakamura
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5404 

Despite high response rates and clinical benefits, androgen ablation therapy does not cure advanced or relapsed prostate cancer, because hormone refractory prostate cancer (HRPC) cells inevitably emerge. There are no effective treatments available for HRPCs, and identification of novel molecular targets and therapeutic approach targeting them are urgently required. We generated the genome-wide gene expression profiles of clinical HRPC cells by using cDNA microarrays combining with laser microbeam microdissection, and identified dozens of trans-activated genes specifically in HRPC cells. Among them, in this study we focused on one novel gene coding a kinase as a molecular target for HRPC. RT-PCR and Northern blot analysis validated its over-expression in HRPC cells and no expression of normal adult organs except prostate and brain. We named it as BPSK (brain-prostate-specific kinase). The antibody specific to BPSK we generated also validated its over-expression in clinical HRPCs, but not in hormone sensitive or naive prostate cancers. Knockdown of BPSK by siRNA resulted in drastic suppression of HRPC cell growth. These findings suggested that BPSK is a promising molecular target for HRPCs, and small molecules specifically inhibiting BPSK can be promising approach for HRPC therapy.
Global Phosphoproteomics Analysis Of Burkitt Lymphoma (BL) Demonstrates Abnormal Protein Phosphorylation In BCR, Spliceosome, mTOR and Chemokine Signaling Pathways In Rituximab Induced Resistant BL
Authors: Aradhana Awasthi, Delphine Rolland, Matthew J. Barth, Janet Ayello, Carmella van de Ven, Myron S. Czuczman, Kojo S.J. Elenitoba-Johnson, Megan Lim, Mitchell S. Cairo
Journal: Blood (2013)
Outcome of patients with borderline ovarian tumors: Results of the multicenter AGO ROBOT study.
Authors: Nikolaus De Gregorio, Klaus H. Baumann, Mignon-Denise Keyver-Paik, Alexander Reuss, Ulrich Canzler, Kerstin Wollschlaeger, Friedrich Kommoss, Dirk Forner, Martin Peters, Willibald Schroeder, Karsten Münstedt, Barbara Richter, Nina Ewald-Riegler, Sven Mahner, Christina Fotopoulou, Barbara Schmalfeldt, Felix Hilpert, Stefan Kommoss, Steffen Hauptmann, Andreas Du Bois
Journal: Journal of Clinical Oncology (2012)

5005 Background: Borderline ovarian tumors (BOT) are a rare entity; current standard of care is based on the available data of predominantly small retrospective trials. Therefore we performed a pattern of care study including central pathology review. Methods: All consecutive patients diagnosed with BOT between 1998 and 2008 in 24 German institutions were included. Tumor samples were prospectively sent for central histopathological review to specialized gynecopathologists, clinical data were collected and patient follow-up was prospectively updated. Results: Pathological review was obtained in 1,042 of 1,236 pts resulting in 950 confirmed BOT cases analyzed here. Under- and overdiagnosis occurred in 3.8% and 5.0% of cases, respectively. Median age was 49 years; 84% of patients had FIGO stage I disease; serous type (S-BOT) was diagnosed in 64% and mucinous type (M-BOT) in 31%. Primary/re-staging surgery led to complete debulking in 92.3% of pts (residual disease 1.3%, unknown 6.4%). Adjuvant chemotherapy was given to 33 (3.5%) pts only. 165 (17%) underwent fertility preserving surgery and 31 (19%) of these patients had documented pregnancies thereafter. Overall, 74 (7.8%) pts experienced relapse and 43 (4.5%) died. Disease progression in the form of invasive carcinoma occurred in 30% of the relapses. Inadequate surgical staging, residual tumor, fertility sparing surgery and higher FIGO stage were associated with shorter progression-free survival (PFS). M-BOT showed a non-significant trend to longer PFS compared to S-BOT (p = 0.07). No differences were observed for laparatomy vs. laparoscopy as initial surgical approach or application of adjuvant chemotherapy. Conclusions: To this day, this is the largest data set available for BOT. Prognosis is favorable even without adjuvant therapy if correct surgical staging is performed. Both tumor characteristics and treatment variables had a significant impact on relapse rate and outcome. In contrast to previous studies, disease progression in the form of invasive carcinoma occurred in a significant amount of patients with relapsed disease.