tbuckley/cabot-search huggingface dataset:
18F-FDG PET/CT in the Detection of Undifferentiated Carcinoma With Osteoclast-like Giant Cells of the Pancreas
Authors: Li-ping Fu, Ai-ping Cheng, Xiao-gang Wang, Jian-lan Fu, Li Jin
Journal: Clinical Nuclear Medicine (2017)

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) is a rare nonendocrine pancreatic tumor. We present a case of a very small UCOGCP. 18F-FDG PET/CT revealed a solid mass measuring 1.0 × 0.8 cm on CT images with an SUVmax of 5.0 in the body of the pancreas. CT revealed a solid mass with significant enhancement. The histopathologic and immunohistochemical studies confirmed the diagnosis. Our findings indicate 18F-FDG PET/CT is a useful imaging modality for UCOGCP diagnosis.
Attitudes regarding privacy of genomic information in personalized cancer therapy.
Authors: Deevakar Rogith, Rafeek Adeyemi Yusuf, Shelly Renee Anstey Hovick, Susan K. Peterson, Allison Michelle Burton-Chase, Yisheng Li, Funda Meric-Bernstam, Elmer Victor Bernstam
Journal: Journal of Clinical Oncology (2013)

9576 Background: Cancer therapy is increasingly personalized to the molecular characteristics of a particular patient and his/her tumor. Patients and providers express interest in personalized therapy yet concerns regarding the privacy of genomic data have been raised, particularly in the context of research. We evaluated patients’ attitudes regarding privacy of genomic data. Methods: Newly registered female breast cancer patients at MD Anderson Cancer Center were invited to participate. Of 308 consecutive patients approached, 100 completed a survey assessing attitudes regarding association of personal identifying information with genomic data, risks for potential insurance and employment discrimination based on genomic information, and willingness to share genomic data (32% response rate). Results: Most patients (83%) indicated that genomic data should be protected. However, only 13% endorsed concern regarding genomic data privacy, measured using a composite scale (α= 0.92). Patients expressed more concern about insurance discrimination than employment discrimination (43% vs. 28%, p&lt;0.001), and these two variables were highly correlated (χ 2 =32.7, p&lt;0.001). Patients expressed greater trust in research institutions like MD Anderson to protect the security of their molecular data compared with government agencies or drug companies (80% vs. 63% vs. 56%; p &lt; 0.001). Most did not endorse concern regarding association of their genomic data with their name and identities (51%), billing and insurance (56%), or clinical data (73%). Patients were more willing to share de-identified data than identified data with researchers other than their treating physicians (p&lt;0.001). 36% of patients were willing to share identified data with any MD Anderson researcher and 14% with any cancer researcher. Conclusions: Patients generally expressed low levels of concern regarding privacy of genomic data. Cancer patients may recognize the clinical and research value of genomic testing and a significant proportion are willing to share their genomic data with researchers.
Effects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial.
Authors: Vasiliki Pelekanou, William E. Barlow, Marie-Kristin von Wahlde, Brad Wasserman, Ying-Chun Lo, Daniel F. Hayes, Gabriel N. Hortobagyi, Julie Gralow, Debu Tripathy, Robert B. Livingston, Peggy Porter, Zeina A. Nahleh, David L. Rimm, Lajos Pusztai
Journal: Journal of Clinical Oncology (2017)

519 Background: Higher baseline TILs and PD-L1 expression are associated with greater pathologic complete response (pCR) rates, but how chemotherapy affects these immune parameters is unknown. The goal of this study was to examine TIL and PD-L1 expression in pre- and post-NAC tumor specimens from the S0800 clinical trial that compared weekly nab-paclitaxel/bevacizumab + dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel + AC as NAC for HER2-negative cases. Association between immune parameters, pCR and NAC-induced changes were tested using ER and NAC-arm adjusted logistic regression. Methods: TILs were assessed on H&amp;E stained full sections of 120 pre- and 62 post-NAC tissues (tumor bed of pCR) including 59 matched samples. PD-L1 immunohistochemistry was performed using the FDA cleared 22C3 assay and results were available for 121 baseline and 43 matched post-NAC samples. Results: At baseline, the mean TIL count was 18%; 16% had no TILs and 9% had &gt; 50% TILs. Higher baseline TILs were associated with higher pCR rate (p = 0.043, trend test p = 0.014) but there was no interaction with NAC arm. Post-NAC, the mean TIL counts was 11%; 5% had no TILs and 1.6% had &gt; 50% TILs. In the matching post-NAC samples, the mean change was 15% decrease in TILs, but in 32% of cases TILs increased. Cases with residual disease (n=44) had lesser average decrease (p=0.029) than cases with pCR (n=15). The post-NAC decrease in TILs was also observed after excluding cases with pCR. At baseline, PD-L1 expression either in the stroma or on epithelial cells or in both was detected in 52 (43%) of 121 cases (5 tumor only, 29 stroma only, 18 tumor + stroma). Those with baseline PD-L1 expression had higher pCR (63% vs. 37%; p=0.008). Post-NAC, PD-L1 expression was seen in 14 of 43 (33%) cases (7 stroma only, 7 tumor + stroma). In the 39 matching pre- and post-NAC samples, PD-L1 expression was negative in both in 20, positive in both in 10 cases and 6 patients had PD-L1 expression at baseline but not in the post-NAC sample. Conclusions: TIL counts and PD-L1 expression generallydecreased, but in a minority of cases increased after NAC. The decrease in TIL was significantly greater in cases achieving pCR. Clinical trial information: NCT00856492.
More Rigorous Study Needed Before Claiming No Harm of Blood Glucose Test Strip Limits for Patients Using Insulin
Authors: Holly O. Witteman
Journal: JAMA Internal Medicine (2017)

To the Editor As an academic investigator living with type 1 diabetes, I have 3 concerns about the article “Association of a Blood Glucose Test Strip Quantity-Limit Policy With Patient Outcomes: A Population-Based Study”1 by Gomes et al published in a recent issue of JAMA Internal Medicine.
Extracellular vesicles in the tumor microenvironment: Therapeutic resistance, clinical biomarkers, and targeting strategies
Authors: L. Han, J. Xu, Q. Xu, B. Zhang, E. W.‐F. Lam, Y. Sun
Journal: Medicinal Research Reviews (2017)

Abstract Numerous studies have proved that cell‐nonautonomous regulation of neoplastic cells is a distinctive and essential characteristic of tumorigenesis. Two way communications between the tumor and the stroma, or within the tumor significantly influence disease progression and modify treatment responses. In the tumor microenvironment (TME), malignant cells utilize paracrine signaling initiated by adjacent stromal cells to acquire resistance against multiple types of anticancer therapies, wherein extracellular vesicles (EVs) substantially promote such events. EVs are nanoscaled particles enclosed by phospholipid bilayers, and can mediate intercellular communications between cancerous cells and the adjacent microenvironment to accelerate pathological proceeding. Here we review the most recent studies of EV biology and focus on key cell lineages of the TME and their EV cargoes that are biologically active and responsible for cancer resistance, including proteins, RNAs, and other potentially essential components. Since EVs are emerging as novel but critical elements in establishing and maintaining hallmarks of human cancer, timely and insightful understanding of their molecular properties and functional mechanisms would pave the road for clinical diagnosis, prognosis, and effective targeting in the global landscape of precision medicine. Further, we address the potential of EVs as promising biomarkers in cancer clinics and summarize the technical improvements in EV preparation, analysis, and imaging. We highlight the practical issues that should be exercised with caution to guide the development of targeting agents and therapeutic methodologies to minimize cancer resistance driven by EVs, thereby allowing to effectively control the early steps of disease exacerbation.
Human T-lymphotropic viruses (HTLV) in England and Wales, 2004 to 2013: testing and diagnoses
Authors: Georgina Ireland, Sara Croxford, Jennifer Tosswill, Rajani Raghu, Katy Davison, Patricia Hewitt, Ruth Simmons, Graham Taylor
Journal: Eurosurveillance (2017)

Human T-lymphotropic virus (HTLV) infection has been under enhanced surveillance in England and Wales since 2002, however, little is known about testing patterns. Using data from two surveillance systems held at Public Health England, we described HTLV antibody testing patterns between 2008 and 2013 and the demographic and clinical characteristics of persons diagnosed with HTLV in England and Wales between 2004 and 2013. An increase in HTLV testing was observed in England between 2008 and 2013 (3,581 to 7,130). Most tests (82%; 7,597/9,302) occurred within secondary care, 0.5% (48/9,302) of persons were reactive for HTLV antibodies and 0.3% (27/9,302) were confirmed positive. Increasing age and female sex were predictors of a reactive HTLV screen and confirmed diagnosis. Testing in primary care including sexual health and antenatal services was infrequent. Between 2004 and 2013, 858 people were diagnosed with HTLV, most of whom were female (65%; 549/851), of black Caribbean ethnicity (60%), not born in the United Kingdom (72%; 369/514) and asymptomatic at diagnosis (45%; 267/595). Despite increased testing, the epidemiology and clinical features of those diagnosed with HTLV have remained consistent. Apart from donor screening, testing for HTLV infection remains uncommon, except to diagnose associated disease.
Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration.
Authors: Qian Shi, Alberto F. Sobrero, Anthony Frank Shields, Takayuki Yoshino, James Paul, Julien Taieb, Ioannis Sougklakos, Rachel Kerr, Roberto Labianca, Jeffrey A. Meyerhardt, Franck Bonnetain, Toshiaki Watanabe, Ioannis Boukovinas, Lindsay A. Renfro, Axel Grothey, Donna Niedzwiecki, Valter Torri, Thierry Andre, Daniel J. Sargent, Timothy Iveson
Journal: Journal of Clinical Oncology (2017)

LBA1 Background: Since 2004, 6 months (m) of oxaliplatin (oxali)-based treatment has been the standard of care as adjuvant therapy for stage III CC. Since oxali is associated with cumulative neurotoxicity, shorter duration of adjuv therapy could spare pts toxicity and lead to substantial saving in health expenditures. Methods: A prospective, pre-planned pooled analysis of 6 concurrently conducted randomized phase III trials (SCOT, TOSCA, Alliance/SWOG 80702, IDEA France (GERCOR/PRODIGE), ACHIEVE, HORG) was performed to evaluate the non-inferiority (NI) of 3m compared with 6m (ref) of adjuv FOLFOX/XELOX. The primary endpoint was disease-free survival (DFS), defined as time from enrolment to relapse, 2 nd CRC, and death (all causes). NI was to be declared if the 2-sided 95% confidence interval (CI) for DFS hazard ratio (HR 3m v 6m) estimated by a stratified Cox model was below 1.12. NI was examined within regimen and stage subgroups as pre-planned. Results: The analysis included 12,834 pts from 12 countries, accrued from 6/07 to 12/15. Stage distribution: 13% T1-2, 66% T3, 21% T4; 28% N2; 40% received XELOX. G3+ neurotoxicity was higher in the 6m v 3m arm (16 v 3% FOLFOX, 9 v 3% XELOX, p&lt;0.0001). With a median follow-up of 39 mos, 3263 DFS events were observed. Overall, the 3 year DFS rate was 74.6% (3m) and 75.5% (6m), with estimated DFS HR of 1.07 (95%CI, 1.00-1.15). The 3m v 6m DFS HRs were 1.16 (95%CI, 1.06-1.26) and 0.95 (95% CI, 0.85-1.06) for FOLFOX and XELOX treated pts, respectively. The 3m v 6m DFS HRs were 1.01 (95%CI, 0.90-1.12) in T1-3 N1, and 1.12 (95%CI, 1.03-1.23) for T4 or N2 pts. Conclusions: While NI was not established for the overall cohort, NI of 3m v 6m oxali-based adjuv therapy was supported for XELOX. As each IDEA trial treated varying proportions of pts with XELOX (0 to 75%), the regimen interaction likely produced the differential outcomes observed between individual studies. Certain substages (T1-3 N1) also showed NI for 3m v 6m. These data provide a framework for discussions on risks and benefits of individualized adjuv therapy approaches. Support: U10CA180821, U10CA180882, U10CA180888, U10CA180835, INCA, PHRC2009, EME 09/800/34, HTA 14/140/84, CRUK C1348/A15960, JFMC. Clinical trial information: NCT01150045.
Detrimental effect of blood-product transfusion on survival for patients with breast cancer in Florida (1996-2007).
Authors: Hattan Alghamdi, Dido Franceschi, Feng Miao, Margaret M Byrne, Tulay Koru-Sengul
Journal: Journal of Clinical Oncology (2015)

1062 Background: There has been a large body of evidence discussing the immunological effects of blood transfusion on survival in patients with a number of different types of cancers. However, few studies have examined the effect of blood transfusion on survival in breast cancer patients and these have had inconsistent results. Methods: Data from Florida Cancer Data System, Agency for Health Care Administration (AHCA), and the US Census were linked for female breast cancer patients in Florida (1996-2007) to understand the association of blood transfusion with female breast cancer patients’ survival. Multivariate regression analyses for overall survival were adjusted for potential confounders related to blood transfusions, including age, gender, race, treatment received, and co-morbidities. Results: Among 120,940 patients identified, 17,686 (14.6%) received blood transfusion during the course of their treatment. The majority of patients were White (90.4%) and non-Hispanics (90.2%); most live in neighborhoods with middle-high (37.9%) and middle-low (29.2%) SES. Patients who had transfusion were older (mean = 66 years), with more advanced SEER stages (24.6% metastasis vs. 20% regional, direct extension±lymph nodes). Transfusion rates were higher in Blacks (18.8%) than in Whites (14.3%) and other races (8.2%). Medicare patients (18.1%) received more blood transfusion compared to private insurance and non-insured population (12%, both). Patients who received chemotherapy (16.8%) had higher rates of blood transfusion compared to the non-chemotherapy group (13.8%). Transfused patients had a shorter overall median survival time (7.7 years) compared to non-transfusion group (12.7 years). Among patients who received transfusion, Blacks, non-Hispanics, and patients with lower SES categories had lower overall median survival. Multivariate analysis indicated that blood transfusion is a significant independent predictor for survival (HR = 1.08;95%CI:1.03,1.13; p < 0.001) after adjusting demographic, clinical, and comorbid factors. Conclusions: Our study concludes that blood transfusion is a significant independent risk factor for survival in female breast cancer patients.
Latent TGF-β–binding protein 4 modifies muscular dystrophy in mice
Authors: Ahlke Heydemann, Ermelinda Ceco, Jackie Lim, Michele Hadhazy, Pearl Ryder, Jennifer Moran, David Beier, Abraham Palmer, Elizabeth Mcnally, Anna Mandinova, Vihren Kolev, Victor Neel, Bing Hu, Wesley Stonely, Jocelyn Lieb, Xunwei Wu, Claudia Colli, Rong Han, Michael Pazin, Paola Ostano, Reinhard Dummer, Janice Brissette, G Dotto
Journal: Journal of Clinical Investigation (2010)
Abstract TMEM-038: THE CULTIVATION AND PARTITIONING OF INVASIVE OVARIAN CANCER CELLS AFTER THEIR ISOLATION FROM WHOLE BLOOD
Authors: Uday K. Veeramallu
Journal: Clinical Cancer Research (2017)

Abstract Ovarian cancer patients suffer from high rates of recurrence and mortality. Circulating tumor cells (CTCs) can serve as a minimally invasive tool to improve the clinical management of such cancer patients. Hence there is growing interest in the isolation, characterization and in vitro culture of CTCs. To this end, the porous membrane cell separators developed by MetaCell s.r.o. provide a simple solution. Ovarian cancer cell line models OVCAR3 and SKOV3 were studied by gene expression profiling and immunostaining for the expression of EPCAM, EGFR, HER2, MET and certain other novel therapeutic targets. Cultivation of the cancer cells after their spike recovery from either cell culture medium or from whole blood was explored using MetaCellTM separators. The cells growing on the separator membranes housed in multi-well culture plates was conveniently visualized with vital cell stains. The SKOV3 cells, but not the OVCAR3 cells, were found to migrate through the membrane pores and populate the well bottoms of the culture plates. This can be attributed to the more plastic and invasive nature of SKOV3 cells as characterized by high Vimentin and low EPCAM expression levels. This is akin to the profile exhibited by highly invasive cancer cells that have undergone epithelial to mesenchymal transition (EMT) and that are implicated in the metastatic spread of cancer in patients. Furthermore, the invasive cells growing on the culture plate well bottoms were found to still stain positively for the therapeutic targets of interest. This cultivation device thus offers the ability to selectively interrogate the more invasive sub-populations within the highly heterogeneous CTCs that are typically seen in cancer patients. After the isolation and cultivation of CTCs, if the partitioned invasive cells remain addressable for the therapeutic target under consideration, the patients are more likely to respond to that therapy for the arrest of metastatic disease. In this context, the MetaCellTM separators have the potential to serve as very effective adjunctive aids for the selection and monitoring of ovarian cancer patients for treatment with targeted therapies. Citation Format: Uday K. Veeramallu, M.S. THE CULTIVATION AND PARTITIONING OF INVASIVE OVARIAN CANCER CELLS AFTER THEIR ISOLATION FROM WHOLE BLOOD [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-038.
Abstract AP14: THERAPEUTIC TARGETING USING TUMOR SPECIFIC PEPTIDES INHIBITS LONG NON–CODING RNA HOTAIR ONCOGENIC ACTIVITY IN OVARIAN CANCER
Authors: Ali R. Özeş, Yinu Wang, Fang Fang, Kenneth P. Nephew
Journal: Clinical Cancer Research (2017)

Abstract PURPOSE: Most women diagnosed with advanced-stage ovarian cancer develop chemo-resistant tumor recurrence, which is uniformly fatal. Long non-coding RNAs (lncRNAs) play key roles in human diseases, including cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA) provide compelling evidence for therapeutic targeting of HOTAIR in ovarian cancer to impact chemoresistance, but targeting lncRNAs in vivo has proven to be difficult. EXPERIMENTAL DESIGN: In the current study, we describe a peptide nucleic acids (PNA)-based approach to effectively block the ability of HOTAIR to interact with EZH2 and subsequently inhibit oncogenic HOTAIR-EZH2 activity. In order to deliver the anti-lncRNA to the acidic (pH approximately 6) microenvironment of solid tumors in vivo, PNAs were conjugated to pH-low insertion peptide (pHLIP). RESULTS: Treatment of HOTAIR-overexpressing ovarian cancer cell lines with PNAs decreased cancer cell invasion and increased chemotherapy sensitivity. The mechanism of action of the anti-lncRNA agent correlated with reduced nuclear factor-kappaB (NF-κB) activation and decreased expression of key NF-κB target genes including matrix metalloprotease 9 and interleukin 6. PNA treatment of ALDH1A1 positive/ovarian tumor initiating cells overexpressing HOTAIR markedly decreased ALDH1A1 activity and reduced the ovarian cancer stem cell population. In mice harboring ovarian tumor xerographs and treated with pHLIP-PNA constructs, HOTAIR oncogenic activity was suppressed, ovarian tumors were resensitized to platinum, and a significant (64%) survival improvement was observed. CONCLUSIONS: Toward developing new therapeutic approaches against chemoresistant ovarian cancer, we designed a PNA-targeting strategy for HOTAIR that effectively blocks the ability of HOTAIR to interact with EZH2 and inhibits oncogenic HOTAIR-EZH2. This first report on pHLIP-PNA targeting HOTAIR in vivo offer pre-clinical proof-of-concept and represents a possible treatment alternative for chemotherapy-resistant ovarian cancer. Citation Format: Ali R. Özeş, Yinu Wang, Fang Fang, and Kenneth P. Nephew. THERAPEUTIC TARGETING USING TUMOR SPECIFIC PEPTIDES INHIBITS LONG NON–CODING RNA HOTAIR ONCOGENIC ACTIVITY IN OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP14.
Abstract 359: Higher ROS Generation and Lower Threshold of mPTP Opening May Underlie Increased Vulnerability of Late Pregnant Heart to Ischemia-Reperfusion Injury
Authors: Jingyuan Li, Andrea Iorga, Ji-Youn Youn, Hua Cai, Vera Regitz-Zagrosek, Mansoureh Eghbali
Journal: Circulation Research (2012)

Although the murine late pregnant (LP) heart is speculated to be a better functioning heart during physiological conditions, the susceptibility of LP hearts to I/R injury is still unknown. The aims of this study were to investigate the cardiac vulnerability of LP rodents to ischemia/reperfusion (I/R) injury and to explore its underlying mechanisms. In-vivo female rat hearts (non-pregnant (NP) or LP) or Langendorff-perfused mouse hearts were subjected to ischemia followed by reperfusion. The infarct size was ∼4 fold larger in LP compared to NP both in the in-vivo rat model and ex-vivo mouse model. The hemodynamic parameters were similar between NP and LP before ischemia. However, the postischemic functional recovery was extremely poor in LP mice comparing to NP mice. RPP was reduced from 12818±1213mmHg*beats/min in NP to 1617± 287mmHg*beats/min in LP mice at the end of reperfusion. Interestingly, all of the hemodynamic parameters almost fully recovered in hearts seven days post-partum (PP7)( RPP= 9604±1215 mmHg*beats/min). To explore the mitochondrial function involvement in the higher vulnerability of LP hearts to I/R injury, mitochondrial respiration and ROS production were measured. Respiratory control index(RCI) were significantly decreased in LP subjected to I/R compared to NP and PP7 (RCI=1.9±0.1 in LP, 4.0±0.5 in NP and 3.9±0.5 in PP7, P&lt;0.05 LP vs. NP and PP7). The superoxide production was also significantly higher in isolated cardiac mitochondria from LP hearts subjected to I/R injury (10.7±1.7mM/min/mg protein in NP; 21.3±3.1mM/min/mg protein in LP and 9.3±3.3mM/min/mg protein in PP7; p&lt;0.05 LP vs. NP and PP7). The threshold for opening of mitochondrial permeability transition pore (mPTP) in response to Ca2+ overload was much lower in LP hearts (calcium retention capacity(CRC)=167±10 nmol/mg-mitochondrial protein) compared with NP (233±18 nmol/mg-mitochondrial protein) and PP7 (260±12 nmol/mg-mitochondrial protein, P&lt;0.01). In conclusion, the higher susceptibility of LP hearts to I/R injury is associated with a lower threshold for triggering the mitochondrial permeability transition pore (mPTP) opening in response to Ca2+ overload which may at least be in part due to higher ROS generation and lower mitochondrial respiration.