tbuckley/cabot-search huggingface dataset:
Human papillomavirus infection and increased risk of breast cancer in north of Iran.
Authors: F. Naghshvar, A. Sigaroodi, S. A. Nadji, G. Janbabaei
Journal: Journal of Clinical Oncology (2011)

28 Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths among women worldwide. Human papillomaviruses have been related to the pathogenesis of breast cancer. In this study, we have analyzed the possible relevance of HPV infection for breast cancer risk among Iranian women from north part of Iran, Mazandaran province. Methods: Polymerase chain reaction method with three different primer sets was applied for detection of HPVs in formalin-fixed paraffin-embedded breast cancer and breast fibroadema as case and control tissues, respectively. HPV genotypes were determined by phylogenetic analysis of viral genome sequences. Results: Of the 58 women with breast cancer, 25.9% (15 isolates) had positive test results for HPV DNA in breast tumor samples in contrast to 2.4% of women (1 out of 41) with non cancer status (P + 0.002). The infection of HPV had an OR of 14.247 (95% CI 1.558-130.284; P + 0.019). The HPV genotypes in samples of breast cancer patients were 26.67% for HPV-16 (4 isolates) and HPV-18 (4 isolates), 13.3% for HPV-23 (2 isolates) and HPV-6 (2 isolates), 6.67% for HPV-11 (1 isolate), HPV-15 (1 isolate) and HPV-124 (1 isolate) and one isolate could not be genotyped compared to HPV reference sequences, while the sole detected HPV in control specimens was HPV-124. Conclusions: Our study reveals that HPV infection and age are the risk factors in breast cancer development in the north part of Iran, Mazandaran province. The association between risk of breast cancer development and viral infection is open and deserves further investigation.
The rate of brain death and organ donation in patients resuscitated from cardiac arrest: a systematic review and meta-analysis
Authors: Claudio Sandroni, Sonia D’Arrigo, Clifton W. Callaway, Alain Cariou, Irina Dragancea, Fabio Silvio Taccone, Massimo Antonelli
Journal: Intensive Care Medicine (2016)

The occurrence of brain death in patients with hypoxic-ischaemic brain injury after resuscitation from cardiac arrest creates opportunities for organ donation. However, its prevalence is currently unknown. Systematic review. MEDLINE via PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews were searched for eligible studies (2002–2016). The prevalence of brain death in adult patients resuscitated from cardiac arrest and the rate of organ donation among brain dead patients were summarised using a random effect model with double-arcsine transformation. The quality of evidence (QOE) was evaluated according to the GRADE guidelines. 26 studies [16 on conventional cardiopulmonary resuscitation (c-CPR), 10 on extracorporeal CPR (e-CPR)] included a total of 23,388 patients, 1830 of whom developed brain death at a mean time of 3.2 ± 0.4 days after recovery of circulation. The overall prevalence of brain death among patients who died before hospital discharge was 12.6 [10.2–15.2] %. Prevalence was significantly higher in e-CPR vs. c-CPR patients (27.9 [19.7–36.6] vs. 8.3 [6.5–10.4] %; p < 0.0001). The overall rate of organ donation among brain dead patients was 41.8 [20.2–51.0] % (9/26 studies, 1264 patients; range 0–100 %). The QOE was very low for both outcomes. In patients with hypoxic-ischaemic brain injury following CPR, more than 10 % of deaths were due to brain death. More than 40 % of brain-dead patients could donate organs. Patients who are unconscious after resuscitation from cardiac arrest, especially when resuscitated using e-CPR, should be carefully screened for signs of brain death.
Beta-2 Microglobulin As a Strong Prognostic Factor in Patients with Diffuse Large B-Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone
Authors: Kazuho Miyashita, Naoto Tomita, Masataka Taguri, Taisei Suzuki, Yasufumi Ishiyama, Yoshimi Ishii, Ayumi Numata, Yukako Hattori, Wataru Yamamoto, Takuya Miyazaki, Takayoshi Tachibana, Hirotaka Takasaki, Kenji Matsumoto, Chizuko Hashimoto, Sachiya Takemura, Etsuko Yamazaki, Katsumichi Fujimaki, Rika Sakai, Shigeki Motomura, Yoshiaki Ishigatsubo
Journal: Blood (2014)
Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN): First overview of complete data set.
Authors: P. M. Harari, A. Y. Chen, W. J. Curran, A. S. Garden, B. A. Murphy, S. J. Wong, L. A. Bellm, M. Schwartz, C. Schneider, K. Ang
Journal: Journal of Clinical Oncology (2010)

5584 Background: We present the first report of overall findings, with mature 1- and 2-year follow up (F/U), from LORHAN, a prospective, longitudinal, observational national registry of head and neck carcinoma (HNC) patients (pts). Dec. 1, 2009 marked the 4th anniversary of LORHAN and a major milestone of enrolling >3,500 pts, triggering this comprehensive analysis. Methods: Pts with newly diagnosed HNC, scheduled to receive radiotherapy (RT) or drug therapy, ≥18 years of age and who have provided written informed consent are eligible for enrollment. Results: As of Jan. 3, 2010, 3525 pts have been enrolled. Nearly 100 community (COM) and academic (ACA) sites from 35 states have enrolled pts in the registry. Of principal investigators participating in LORHAN, 22% designated their setting as ACA, 78% as COM. ACA centers accrued 65% of pts. Locked records (signed off by the investigator) are available as follows: baseline (n=2,924), initial cancer treatment (tx) (n=2,276), re-tx (n=380), year (yr)-1 F/U (n=1,304) and yr-2 F/U (n=497). Few pts (n=67) are lost to F/U. Compared to COM sites, ACA centers treated younger pts, more black and fewer white pts, pts with poorer performance status, fewer laryngeal but more oropharyngeal, paranasal sinus and nasal tumors, and more advanced disease (all p-values <0.05); other clinical features were similar. More than half (56%) of pts received concurrent chemoradiation (CRT), either following curative surgery (n=335), induction chemotherapy (n=67) or alone (n=813). IMRT was the most common form of RT delivered (83% overall) and was used more frequently at ACA centers (89% vs. 74%; p<0.0001). Most common cancer drugs delivered were single-agent cisplatin (49% of pts), cetuximab (21%) and carboplatin/paclitaxel (7%); cisplatin was used more often at ACA sites, while cetuximab was used more often in the COM (all p-values < 0.05). The 1- and 2-yr rates for locoregional control were 85% and 74% and for overall survival were 85% and 73%, respectively. Conclusions: LORHAN provides important insights regarding U.S. patterns of practice and tx outcomes for HNC pts. As the sample size grows, LORHAN will be increasingly suited for conducting hypothesis-driven, population-based research. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedNet Solutions Bristol-Myers Squibb, ImClone Systems, MedNet Solutions Bristol-Myers Squibb, Merck Serono Amgen, Cellectar, Genentech, ImClone Systems
A phase I study of DX 8951f (exatecan mesylate for injection) in patients with renal dysfunction
Authors: C. J. Sweeney, M. W. Saif, P. M. Lorusso, M. P. Ducharme, R. Demnati, M. Danna, E. Rowinsky, M. Mita, R. Dejager, C. Takimoto
Journal: Journal of Clinical Oncology (2004)

2069 Background: Exatecan mesylate is a novel camptothecin analog. Neutropenia and thrombocytopenia are its dose limiting toxicities (DLTs). Although the drug appears to be predominately cleared by the liver, the impact of renal dysfunction on its pharmacokinetic profile is unknown. Methods: A dose escalation study was performed with patients (pts) treated in pre-defined cohorts of renal dysfunction determined by 24-hour measured urine creatinine clearance - CrCL (Table 1). Once a DLT was observed, pts were stratified by prior therapy (heavily pre-treated-HP versus minimally pre-treated- MP). Exatecan was given daily x 5 every 21 days. Results: 32 pts have been accrued to this study. The number of DLT events observed for each group are: Normal - 1/6 pts at 0.5 mg/m2; Mild −1/7 HP pts at 0.4 mg/m2; Moderate −1/3 HP pts and 0/3 MP pts at 0.4 mg/m2and 1/1 MP pt at 0.5 mg/m2; Severe −0/2 HP pts at 0.1 mg/m2. The mean total CL of exatecan per body surface area (BSA) for each group is presented in Table 1 and reported based on three different measurements of renal function. Each method has distinct advantages and disadvantages. The calculated CrCL is most applicable to clinical practice, while the Technitium GFR method is the most precise way of estimating GFR. Preliminary PK results tend to suggest that the CL of exatecan is similar between moderately impaired and normal subjects when stratifying patients according to their calculated CrCL, while the technitium GFR method seems to indicate that the CL of exatecan is the same between mild, moderate and severely impaired patients. Conclusions: The preliminary PK data suggests that dosage adjustments may not be necesssary for patients with renal dysfunction. The clinical data supports this as patients with mild or moderate dysfunction tolerate at least 0.4 mg/m2. Further recruitment to the moderate and severe dysfunction groups is ongoing to further explore these findings. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi Daiichi Daiichi
Adventitial Delivery of an Allogeneic Bone Marrow–Derived Adherent Stem Cell in Acute Myocardial Infarction
Authors: Marc S. Penn, Stephen Ellis, Sanjay Gandhi, Adam Greenbaum, Zachary Hodes, Farrell O. Mendelsohn, David Strasser, Anthony E. Ting, Warren Sherman
Journal: Circulation Research (2011)

Rationale: MultiStem is an allogeneic bone marrow–derived adherent adult stem cell product that has shown efficacy in preclinical models of acute myocardial infarction (AMI). In this phase I clinical trial in patients with first ST-elevation–myocardial infarction (STEMI), we combine first-in-man delivery of MultiStem with a first-in-coronary adventitial delivery system to determine the effects of this system on left ventricular function at 4 months after AMI. Objective: Test the effects of adventitial delivery of Multistem in the peri-infarct period in patients with first STEMI. Methods and Results: This study was a phase I, open-label, dose-escalating registry control group study. Nineteen patients received MultiStem (20 million, n=6; 50 million, n=7; or 100 million, n=6) and 6 subjects were assigned to the registry control group. Two to 5 days after AMI, we delivered MultiStem to the adventitia of the infarct-related vessel in patients with first-time STEMI. All patients underwent primary percutaneous coronary intervention with resulting Thrombolysis In Myocardial Infarction grade 3 flow and with ejection fraction (EF) ≤45% as determined by echocardiogram or left ventriculogram within 12 hours of primary percutaneous coronary intervention. The cell product (20 million, 50 million, or 100 million) was well tolerated, and no serious adverse events were deemed related to MultiStem. There was no increase in creatine kinase-MB or troponin associated with the adventitial delivery of MultiStem. In patients with EF determined to be ≤45% by a core laboratory within 24 hours before the MultiStem injection, we observed a 0.9 (n=4), 3.9 (n=4), 13.5 (n=5), and 10.9 (n=2) percent absolute increases in EF in the registry, 20 million, 50 million, and 100 million dose groups, respectively. The increases in EF in the 50 million and 100 million groups were accompanied by 25.4 and 8.4 mL increases in left ventricular stroke volume. Conclusions: In this study, the delivery of MultiStem to the myocardium in patients with recent STEMI was well tolerated and safe. In patients who exhibited significant myocardial damage, the delivery of ≥50 million MultiStem resulted in improved EF and stroke volume 4 months later. These findings support further development of MultiStem in patients with AMI and they validate the potential of a system for delivery of adult stem cells at any time after primary percutaneous coronary intervention.
Twenty-four–Month Outcomes of the Ranibizumab for Edema of the Macula in Diabetes – Protocol 3 with High Dose (READ-3) Study
Authors: Yasir J. Sepah, Mohammad Ali Sadiq, David Boyer, David Callanan, Ron Gallemore, Michael Bennett, Dennis Marcus, Lawrence Halperin, Muhammad Hassan, Peter A. Campochiaro, Quan Dong Nguyen, Diana V. Do, Diana V. Do, Dennis Marcus, Eugene Lit, Erik Kruger, John Pollack, Larry Halperin, Michael Bennett, Ron Gallemore, David Boyer, David Callanan, Kang Zhang, Andrew Symons, Prema Abraham, David Boyer, David G. Callanan, Peter A. Campochiaro, Quan Dong Nguyen, Brian P. Conway, David J. Wilson, Yasir Jamal Sepah, Mohammad Ali Sadiq, Mostafa Hanout, Muhammad Hassan, Aniruddha Agarwal, Rubbia Afridi, Lisa Greer, Mohammad Ali Sadiq, Yasir Jamal Sepah
Journal: Ophthalmology (2016)
Analysis of D7S486 in primary gastric cancer and evaluation of TESTIN as a candidate tumor suppressor gene.
Authors: J. Xia, D. Weng, H. Ma, Y. Chen, W. Huang, K. Pan
Journal: Journal of Clinical Oncology (2010)

4129 Background: Gastric cancer (GC) is one of the most common malignancies in Asia. High frequency of loss of heterozygosity (LOH) was found on D7S486 in primary GC, suggesting some tumor suppressor genes (TSGs) harbored in this region. Methods: To determine what GC-associated TSGs were located in this region, we analyzed the LOH at D7S486 in 105 patients with primary GC through a high-flux single nucleotide polymorphism (SNP) scan by self-made SNP microarray technology. To clarify the role of TESTIN (TES) in GC, we examined its expression in primary GC and its relationship to clinicopathological characteristics and prognosis. In addition, we also studied the effect of TES overexpression on the proliferation of several GC cell lines. Furthermore, mutation and methylation analysis were performed to explore its possible mechanisms of inactivation in GC. Results: We discovered five candidate genes (ST7Å, FOXP2Å, MDFIC, TES and CAV1) corresponding to SNPs whose frequencies of LOH were higher than 30%. However, only TES showed the potential to be a TSG associated with GC. In primary GC, TES showed a significant low expression in both transcriptive and translational level when compared to adjacent nontumorous tissues. In addition, down regulation of TES was shown to correlate with differentiation and prognosis. We also determined the inhibitory effect of TES overexpression on the growth of three GC cell lines. Methylation analysis showed that hypermethylation of TES promoter was a frequent event in primary GC samples and GC cell lines in which TES expression was down regulated. However, no specific gene mutation was observed in the coding region of the TES gene. Conclusions: Collectively, these results support the role of TES as a TSG in gastric carcinogenesis and that TES is inactivated primarily by transcriptional silencing resulting from CpG island methylation rather than by gene mutation. No significant financial relationships to disclose.
Can induction chemotherapy improve dysphagia in locally advanced esophageal/GEJ cancer?
Authors: Elizabeth Won, David H. Ilson, Jessica Herrera, Yelena Yuriy Janjigian, Geoffrey Yuyat Ku, Nabil P. Rizk, Inderpal S. Sarkaria, Prasad S. Adusumili, Valerie W. Rusch, Manjit S. Bains
Journal: Journal of Clinical Oncology (2014)

148 Background: Dysphagia is one of the most common presenting symptoms in esophageal cancer (EC) and can lead to significant nutritional decline, which is associated with increased toxicity and poor outcomes. Invasive feeding tubes or endoscopic stents are frequently used to improve nutrition in this setting. We evaluated the role of induction chemotherapy prior to concurrent chemoradiation as presurgical treatment in improving dysphagia. Methods: Retrospective analysis of 4 prospective studies conducted at MSKCC with induction chemotherapy followed by concurrent chemoradiation and surgery in locally advanced esophageal/GEJ cancer. Regimens included cisplatin/paclitaxel, cisplatin/irinotecan, and cisplatin/irinotecan/bevacizumab. Dysphagia was graded prospectively using a validated dysphagia scale. Response of dysphagia and nutritional status to induction chemotherapy was evaluated. Results: Of 161 patients (pts) undergoing induction chemotherapy, [median age 59(21-76), KPS 90 (70-100), 77% adenocarcinoma], 121 (76%) had dysphagia, with 59(37%) having grade 2 dysphagia or higher (20% Stage II, 80% Stage III). 6(4%) required EGD dilatation/stent and none required feeding tube placement prior to treatment. 22% patients had&gt;10% body weight loss prior to treatment and average weight loss in all pts was 4.3kg. After induction chemotherapy, 104 (64%) had improvement in dysphagia. This was associated with a weight gain in 42% of pts. Only 7(4%) had worsening dysphagia after induction chemotherapy: 4/7 required feeding tubes (2% of all pts), 2/7 underwent endoscopic dilatation or stent (1% of all pts). 6/7 of these pts with worsening dysphagia had poor short term outcomes after induction treatment: 2/7 progressive disease, 3/7 unresectable at surgery, 1/7 post-operative death. Conclusions: Induction chemotherapy prior to concurrent chemoradiation for locally advanced esophageal cancer can effectively improve swallowing and nutritional status, while mitigating need for feeding tubes or stents in patients with significant dysphagia. Post-induction dysphagia may be prognostic and merits further investigation.
PHA-680626 Exhibits Anti-Proliferative and Pro-Apoptotic Activity on Imatinib-Resistant Chronic Myeloid Leukemia Cell Lines and Primary CD34+ Cells by Inhibition of Both Bcr-Abl Tyrosine Kinase and Aurora Kinases.
Authors: Artur Gontarewicz, Stefan Balabanov, Gunhild Keller, Jens Panse, Mirja Bernhardt, Carsten Bokemeyer, Walter Fiedler, Jurgen Moll, Tim Brummendorf
Journal: Blood (2007)
Phase II study of fixed-dose-rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced bile duct cancer: Daegu Gyeoungbuk Oncology Group.
Authors: H. Ryoo, S. Bae, M. Kim, K. H. Lee, H. Song, Y. Chae, W. Lee, J. Baek
Journal: Journal of Clinical Oncology (2011)

280 Background: This phase II study evaluated efficacy of fixed dose rate (FDR) infusion of gemcitabine (10mg/m 2 /min) and UFT combination in chemo-naïve patients with advanced bile duct cancer. Methods: This was an open-label, single-arm, multicenter, phase II study with a Simon two-stage minimax design. Patients received the FDR gemcitabine 1,000mg/m 2 for 3 consecutive weeks and UFT 400 mg/m 2 on days 1-21. The cycle was repeated every 28 days. The primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) -defined objective response rate. Secondary end points included clinical benefit response (CBR), safety, progression-free survival (PFS), and overall survival (OS). Clinical characteristics including four single nucleotide polymorphisms in DNA repair genes (RecQ1, RAD54L, XRCC1, ATM) were evaluated whether these influence the overall survival. Results: Between December 2006 and February 2008, fifty-one patients were enrolled, with a median age of 58 years. The majority of patients (76%) had intra-hepatic disease. Fourteen patients (27%) had a RECIST investigator-assessed, partial response (PR); disease control rate (PR + stable disease) was 55%. CBR was 14% among 37 evaluable patients. Hematologic toxicity was main grade 3 or 4 treatment-related adverse events. Median PFS was 4.0 months (95% CI, 2.9 to 5.1 months). Median OS was 7.0 months (95% CI, 3.5 to 10.5 months). Intrahepatic disease, poor performance, and, XRCC1 R194W C/C type were predictive markers of poor overall survival. Conclusions: FDR gemcitabine and UFT demonstrated apparent activity in patients with advanced bile duct cancer. However, this activity did not translate to prolong survival. The location of disease, performance status, and, polymorphic variants of DNA repair genes may affect clinical outcome of patients with advanced bile duct cancer. No significant financial relationships to disclose.
Maintenance of clinical efficacy following dose reduction of ixabepilone plus capecitabine (Cape) in patients (pts) with anthracycline (A) and taxane (T) pretreated (pretx) metastatic breast cancer (MBC): A retrospective analysis of pooled data from two phase III clinical studies (046/048).
Authors: V. Valero, L. D. Bosserman, D. A. Yardley, H. H. Roche, E. Thomas, L. T. Vahdat, P. Mukhopadhyay, D. M. Opatt, R. A. Peck, J. Sparano
Journal: Journal of Clinical Oncology (2010)

1051 Background: Ixabepilone 40 mg/m2 (ixabepilone 40) is approved in combination with Cape for treatment of MBC, but this dose may subsequently be reduced to 32 mg/m2 to manage toxicity. Anecdotal evidence suggests that in combination with Cape, efficacy is maintained following dose reduction from ixabepilone 40 to 32, but clinical data have yet to support this observation. Methods: 1,973 pts with MBC pretx with A and T were randomized to receive Cape alone 1,250 mg/m2 or ixabepilone 40 plus Cape 1,000 mg/m2 D1-14 every 3 weeks. Due to the similarity of the study design and pt populations from both studies, data were pooled for this analysis. Pts in the combination arm who underwent dose reduction in the first 4 courses (early reductions) were retrospectively compared to pts who remained on ixabepilone 40 or underwent dose reduction after 4 courses (no/late reductions). To adjust for bias resulting from selecting pts with inherently better outcome based on duration of therapy, these analyses were restricted to pts who received ≥4 courses of ixabepilone treatment. Results: 566 pts were considered for this analysis. ORR and PFS were comparable in pts who had early versus late/no dose reductions of ixabepilone. Conclusions: These data suggest that ixabepilone dose reductions did not impact the overall efficacy of MBC pts treated with ixabepilone plus Cape. Ixabepilone 40with early reduction Ixabepilone 40 with late/no reduction N = 347* N > 219* ORR, % 55.3 62.6 (95% CI) (49.9–60.6) (55.8–69.0) PFS (mo), median 7.0 7.2 (95% CI) (6.5–7.5) (6.6–8.0) HR (95% CI) 0.98 (0.83–1.17) * Only pts with measurable disease were included. All pts received ≥4 courses of ixabepilone. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb