tbuckley/cabot-search huggingface dataset:
The time for Epstein-Barr virus Latent Membrane Protein-1 (EBV LMP-1) to disappear after initiation of primary radiotherapy is an independently significant prognostic factor predicting local control for the patients with nasopharyngeal carcinoma (NPC)
Authors: Ngan M. Tsang, Shinn Y. Lin, Ping C. Pai, Chen K. Tseng
Journal: Cancer Research (2005)

2156  Purpose: The presence of EBV LMP-1 in the nasopharyngeal swab specimens indicates the presence of NPC tumor cells; likewise, the disappearance of EBV LMP-1 implies the eradication of mucosal NPC tumor cells. Hypothetically, the faster this biological marker takes to disappear, the better NPC local control could be achieved after standard treatment. This study was undertaken to investigate whether the time for EBV LMP-1 to disappear after initiation of primary RT was inversely associated with NPC local control Method and Materials: During July 1999 and October 2002, there were 127 NPC patients without distant metastasis at initial diagnosis receiving serial examinations of nasopharyngeal swabbing with detection of EBV LMP-1 during the course of radiotherapy and thereafter and totally 972 specimens were collected. At least five specimens were obtained from each studied patient and a minimal 2-year follow-up is required for eligibility. The time of LMP-1 regression was defined as the days after the initiation of radiotherapy when the LMP-1 result turned out to be negative. The primary outcome representing NPC local control was the time to develop local relapse. It was calculated as the duration from the date of the initiation of radical radiotherapy to the date of diagnosing local recurrence. Cumulative local recurrence-free rates were calculated by the Kaplan-Meier method and compared by log-rank test. Result: The time for LMP-1 to disappear after initiation of primary RT did show a statistically significant influence on NPC local control which was represented by the time to develop local recurrence during the follow-up period in both univariable (hazard ratio, 1.028; 95 % confidence interval, 1.016 - 1.041; p
BET Inhibition as a Rational Therapeutic Strategy for Invasive Lobular Breast Cancer
Authors: Louise Walsh, Kathryn E. Haley, Bruce Moran, Brian Mooney, Finbarr Tarrant, Stephen F. Madden, Alessandra Di Grande, Yue Fan, Sudipto Das, Oscar M. Rueda, Catríona M. Dowling, Damir Varešlija, Suet-Feung Chin, Sabine Linn, Leonie S. Young, Karin Jirström, John P. Crown, Rene Bernards, Carlos Caldas, William M. Gallagher, Darran P. O'Connor, Tríona Ní Chonghaile
Journal: Clinical Cancer Research (2019)

Invasive lobular carcinoma (ILC) is a subtype of breast cancer accounting for 10% of breast tumors. The majority of patients are treated with endocrine therapy; however, endocrine resistance is common in estrogen receptor-positive breast cancer and new therapeutic strategies are needed. Bromodomain and extraterminal inhibitors (BETi) are effective in diverse types of breast cancer but they have not yet been assessed in ILC.
Focused ultrasound activates voltage-gated calcium channels through depolarizing TRPC1 sodium currents in kidney and skeletal muscle
Authors: Scott R. Burks, Rebecca M. Lorsung, Matthew E. Nagle, Tsang-Wei Tu, Joseph A. Frank
Journal: Theranostics (2019)

Pulsed focused ultrasound (pFUS) technology is being developed for clinical neuro/immune modulation and regenerative medicine. Biological signal transduction of pFUS forces can require mechanosensitive or voltage-gated plasma membrane ion channels. Previous studies suggested pFUS is capable of activating either channel type, but their mechanistic relationship remains ambiguous. We demonstrated pFUS bioeffects increased mesenchymal stem cell tropism (MSC) by altering molecular microenvironments through cyclooxygenase-2 (COX2)-dependent pathways. This study explored specific relationships between mechanosensitive and voltage-gated Ca2+ channels (VGCC) to initiate pFUS bioeffects that increase stem cell tropism. Methods: Murine kidneys and hamstring were given pFUS (1.15 or 1.125 MHz; 4MPa peak rarefactional pressure) under ultrasound or magnetic resonance imaging guidance. Cavitation and tissue displacement were measure by hydrophone and ultrasound radiofrequency data, respectively. Elastic modeling was performed from displacement measurements. COX2 expression and MSC tropism were evaluated in the presence of pharmacological ion channel inhibitors or in transient-receptor-potential-channel-1 (TRPC1)-deficient mice. Immunohistochemistry and co-immunoprecipitation examined physical channel relationships. Fluorescent ionophore imaging of cultured C2C12 muscle cells or TCMK1 kidney cells probed physiological interactions. Results: pFUS induced tissue deformations resulting in kPa-scale forces suggesting mechanical activation of pFUS-induced bioeffects. Inhibiting VGCC or TRPC1 in vivo blocked pFUS-induced COX2 upregulation and MSC tropism to kidneys and muscle. A TRPC1/VGCC complex was observed in plasma membranes. VGCC or TRPC1 suppression blocked pFUS-induced Ca2+ transients in TCMK1 and C2C12 cells. Additionally, Ca2+ transients were blocked by reducing transmembrane Na+ potentials and observed Na+ transients were diminished by genetic TRPC1 suppression. Conclusion: This study suggests that pFUS acoustic radiation forces mechanically activate a Na+-containing TRPC1 current upstream of VGCC rather than directly opening VGCC. The electrogenic function of TRPC1 provides potential mechanistic insight into other pFUS techniques for physiological modulation and optimization strategies for clinical implementation.
The BMP‐SMAD pathway mediates the impaired hepatic iron metabolism associated with the ERFE‐A260S variant
Authors: Immacolata Andolfo, Barbara Eleni Rosato, Roberta Marra, Gianluca De Rosa, Francesco Manna, Antonella Gambale, Achille Iolascon, Roberta Russo
Journal: American Journal of Hematology (2019)

Abstract The erythroferrone (ERFE) is the erythroid regulator of hepatic iron metabolism by suppressing the expression of hepcidin. Congenital dyserythropoietic anemia type II (CDAII) is an inherited hyporegenerative anemia due to biallelic mutations in the SEC23B gene. Patients with CDAII exhibit marked clinical variability, even among individuals sharing the same pathogenic variants. The ERFE expression in CDAII is increased and related to abnormal erythropoiesis. We identified a recurrent low‐frequency variant, A260S, in the ERFE gene in 12.5% of CDAII patients with a severe phenotype. We demonstrated that the ERFE‐A260S variant leads to increased levels of ERFE, with subsequently marked impairment of iron regulation pathways at the hepatic level. Functional characterization of ERFE‐A260S in the hepatic cell system demonstrated its modifier role in iron overload by impairing the BMP/SMAD pathway. We herein described for the first time an ERFE polymorphism as a genetic modifier variant. This was with a mild effect on disease expression, under a multifactorial‐like model, in a condition of iron‐loading anemia due to ineffective erythropoiesis.
A Decade of Anti-Myeloma Vaccine Development through Early Phase Trials: A Systematic Review
Authors: Nadia Carenina Nunes Cavalcante Parr, Muhammad Junaid Tariq, Muhammad Usman, Muhammad Asad Fraz, Ali Younas Khan, Sharoon Samuel, Awais Ijaz, Malik Qistas Ahmad, Muhammad Jahanzeb Khalil, Muhammad Yasir, Saher Nasir Amin, Ahmad Safdar, Abdul Rafae, Faiz Anwer
Journal: Blood (2018)
The great debate at “Immunotherapy Bridge 2018”, Naples, November 29th, 2018
Authors: Paolo A. Ascierto, Lisa H. Butterfield, Sandra Demaria, Robert L. Ferris, Gordon J. Freeman, Roger S. Lo, Alberto Mantovani, Paul Nathan, Omid Hamid, Katerina Politi, Igor Puzanov
Journal: Journal for ImmunoTherapy of Cancer (2019)

As part of the 2018 Immunotherapy Bridge congress (November 28–29, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on four topical clinical issues in immunotherapy today. These were: the relative importance of adaptive versus innate immunity in the anti-cancer immune response; the merits of combination versus sequential immunotherapy regimens in the treatment of cancer; the advantages and disadvantages of murine models of cancer versus humans in order to evaluate immunotherapy; and whether or not mechanisms of resistance to immunotherapy differ between different cancers. Discussion of these important topics are summarised in this report.
The comparison of accuracy between PET and PET/CT for detecting lymph node metastasis in cervical cancer: Prospective surgicopathologic study
Authors: J. Park, S. Seo, S. Kang, S. Lim, M. Lim, H. Choi, S. Kim, C. Yoo, J. Kim, S. Park
Journal: Journal of Clinical Oncology (2007)

5587 Background: Previosly, we reported the accuracy of positron emission tomography with 2-[fluorine18] fluoro-2-deoxy-D- glucose (FDG-PET) for detecting metastatic lymph node (LN) in cervical cancer (Eur J Cancer 2005: 41; 2086–92). The aim of this prospective study was to evaluate the accuracy of PET/CT for detecting lymph node metastasis in cervical cancer and to compare the accuracy between PET and PET/CT. Methods: From May 2002 to Jul 2006, 86 patients with untreated stage IB-IVA cervical cancer were enrolled. All patients underwent pretreatment clinical staging including PET (May 2002-Aug 2003, 54 patients) or PET/CT (Jan 2004-Jul 2006, 32 patients) followed by surgical staging including systematic pelvic and paraaortic lymph node (PLN and PALN) dissection. To enable region specific comparisons, PALN and PLN were divided into eight regions: both PALN, both common iliac areas, both external iliac areas, and both internal iliac/obturator areas. Each lymph node was sliced at 2-mm intervals perpendicular to the greatest dimension to maximize the likelihood of detecting micrometastases. All metastatic tumor size in each involved lymph node was measured. Histopathologic evaluation of lymph nodes was the diagnostic standard. The study protocol was approved by Institutioal Review Board, and a written informed consent was obtained. Results: A total of 688 LN regions were evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value of PET and PET/CT are shown in Table 1 . As the metastatic tumor size increased, the sensitivity of PET and PET/CT was improved. Although there were no differences in sensitivity for detecting large sized (&gt; 5mm or 10mm) metastatic tumor, PET/CT was more sensitive than PET for all pathologically proven LN metastasis which included small sized (&lt; 5mm) metastatic tumor. Conclusions: PET/CT was more sensitive than PET for detecting small sized (&lt;5mm) lymph node metastasis in cervical cancer. [Table: see text] No significant financial relationships to disclose.
Abstract #553: MiRNA expression profiling and validation in formalin-fixed paraffin-embedded breast cancer tissue
Authors: Yingchun Zhao, Jing Xiao, Hengwei Zhang, Rui Cao, Caishu Deng, Zoran Gatalica, Ed Silva, Robert Recker, Gary Xiao
Journal: Cancer Research (2009)

MiRNAs emerge as important regulators in tumorigenesis. We extracted total RNA from formalin-fixed paraffin-embedded tissues of different breast cancer stages and applied µParaflo\#8482; human MiRNA microarray to screen for deregulated miRNAs. A total of 14 miRNAs were found to be deregulated in breast cancer development. Among them, miR-21 and let-7i were validated by realtime PCR and in situ hybridization as real oncomirs for the progression of benign, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) stages. Future work will include target gene identification and in vivo animal study.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 553.
Combination of Surgery With Extensive Intraoperative Peritoneal Lavage for Patients With Advanced Gastric Cancer
Authors: Thales Paulo Batista
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Enhanced in vivo drug-linker stability of an anti-CD70 auristatin immunoconjugate
Authors: Russell J. Sanderson, Stephen C. Alley, Scott C. Jeffrey, Charles G. Cerveny, Roger F. Zabinski, Ivan Stone, Dennis Benjamin, Peter D. Senter
Journal: Cancer Research (2006)

1991  Antibody-drug conjugates (ADC) with linker systems that are highly stable in circulation provide an effective and efficient means of delivering drug to antigen-positive cells. We have previously described ADCs conjugated to the potent anti-mitotic agents monomethylauristatin E and F (MMAE and MMAF), through a protease-sensitive valine-citrulline dipeptide linker. The thiol-reactive drug-linkers used for the preparation of these ADCs, maleimidocaproyl-val-cit-p-aminobenzyloxycarbamyl-MMAE and MMAF (mc-val-cit-MMAE and -MMAF), efficiently released drug in lysosomes of target cells and yielded potent ADCs. Subsequent evaluation of an anti-CD30 immunoconjugate in mouse circulation demonstrated that the half-life of the conjugated drug-linker was about 6 days. To build drug linkers with higher stability, we have prepared bromoacetamidocaproyl-MMAF (bac-MMAF) and conjugated it to the humanized anti-CD70 mAb, h1F6-C4A, with a homogenous loading of 4 drugs per antibody. Despite the lack of a protease-sensitive linker, this ADC was highly active in vitro and in vivo at well tolerated doses. ELISA-based methods were developed to investigate the drug-linker stability in rodents. Loss of the bromoacetimide-coupled drug-linker was not observed after 15 days in systemic circulation. These drug-linkers provide enhanced stability and have significant potential to improve the therapeutic window of auristatin ADCs used for the treatment of cancer.
Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer
Authors: Anna F. Farago, Beow Y. Yeap, Marcello Stanzione, Yin P. Hung, Rebecca S. Heist, J. Paul Marcoux, Jun Zhong, Deepa Rangachari, David A. Barbie, Sarah Phat, David T. Myers, Robert Morris, Marina Kem, Taronish D. Dubash, Elizabeth A. Kennedy, Subba R. Digumarthy, Lecia V. Sequist, Aaron N. Hata, Shyamala Maheswaran, Daniel A. Haber, Michael S. Lawrence, Alice T. Shaw, Mari Mino-Kenudson, Nicholas J. Dyson, Benjamin J. Drapkin
Journal: Cancer Discovery (2019)

Abstract Small-cell lung cancer (SCLC) is an aggressive malignancy in which inhibitors of PARP have modest single-agent activity. We performed a phase I/II trial of combination olaparib tablets and temozolomide (OT) in patients with previously treated SCLC. We established a recommended phase II dose of olaparib 200 mg orally twice daily with temozolomide 75 mg/m2 daily, both on days 1 to 7 of a 21-day cycle, and expanded to a total of 50 patients. The confirmed overall response rate was 41.7% (20/48 evaluable); median progression-free survival was 4.2 months [95% confidence interval (CI), 2.8–5.7]; and median overall survival was 8.5 months (95% CI, 5.1–11.3). Patient-derived xenografts (PDX) from trial patients recapitulated clinical OT responses, enabling a 32-PDX coclinical trial. This revealed a correlation between low basal expression of inflammatory-response genes and cross-resistance to both OT and standard first-line chemotherapy (etoposide/platinum). These results demonstrate a promising new therapeutic strategy in SCLC and uncover a molecular signature of those tumors most likely to respond. Significance: We demonstrate substantial clinical activity of combination olaparib/temozolomide in relapsed SCLC, revealing a promising new therapeutic strategy for this highly recalcitrant malignancy. Through an integrated coclinical trial in PDXs, we then identify a molecular signature predictive of response to OT, and describe the common molecular features of cross-resistant SCLC. See related commentary by Pacheco and Byers, p. 1340. This article is highlighted in the In This Issue feature, p. 1325
Stromal cell derived factor-1α and macrophages increased invasive potential of breast cancer cells expressing CXCR4
Authors: Devin D. Twitchell, Seiga Ohmine, Thaidra A. Gaufin, Russell L. Hamblin, Kim L. O’Neill, Byron K. Murray
Journal: Cancer Research (2005)

4694  Chemokines are involved in the regulation of cellular processes including those in migration, invasion and angiogenesis. CXCR4/Stromal-cell derived factor-1α (SDF-1α) interactions have been demonstrated to play pivotal roles in metastasis and chemotaxis. Increasing evidence suggests that tumor associated macrophages may contribute to cancer progression by altering the tumor microenvironment through the release of angiogenic, proteolytic and epidermal growth factors. Metastatic breast cancer cells may undergo a series of morphological changes, including cell polarization and extension of invadopodia, followed by migration from the primary tumor site and the induction of neovascularization. Many of these changes are associated with dynamic actin rearrangement and activation of signaling pathways through transmembrane receptors, including G-protein-coupled receptors and chemokine receptors. In association with cell adhesion molecules located on the cell membrane, the cytoskeleton affects the quality of cell-to-cell and cell-to-substrate interactions mediated by integrins that are associated with extracellular matrix proteins. In the present study, we report that MDA-MB-231 breast adenocarcinoma cells polarize and migrate in the presence of SDF-1α and macrophages. Cells were cultured in a BD Matrigel™ basement membrane matrix (4.8 mg/ml protein content), with or without SDF-1α (100 ng/ml). U937 monocytic cells were differentiated into macrophages following a 12-hour treatment with 10 ng/ml of phorbol myristate acetate and co-cultured with MDA-MB-231 cells. Cell invasion, migration and membrane extensions were analyzed by confocal microscopy and the FLUOview FV300 analysis software. Polarization, migration and dynamic morphological changes were observed following exposure to SDF-1α, macrophages or in the presence of both. Cell polarization and invasion XY scan and Z scan images were acquired and migration was quantified in the x, y and z-axis. MDA-MB-231 control cells migrated approximately 5 μm, while MDA-MB-231, in the presence of macrophages, showed a two-fold increase in migration. SDF-1α containing matrigel showed the greatest increase in migration at 20.5 μm. The results show that MDA-MB-231 breast adenocarcinoma cells polarize and migrate in the presence of macrophages and enhance further migration in the presence of SDF-1α. Other breast adenocarcinoma cells expressing high and low levels of CXCR4 are currently under investigation.
Pediatric cancer incidence and survival in the United States (1973-2003)
Authors: Amy Linabery, Julie Ross
Journal: Cancer Research (2007)

65  Over 12,000 children are newly diagnosed with malignancy each year in the United States. Cancer is the leading cause of disease-related mortality in children between the ages of 1-19 years. Unfortunately, the etiology of most childhood cancers is unknown. Recent reports from Europe suggest that both pediatric cancer incidence and survival has been increasing over the last several decades. We examined population-based incidence and survival data from the Surveillance, Epidemiology, and End Results (SEER) program to provide updated information regarding United States incidence and survival trends. Data were obtained on incident cancers diagnosed in children under the age of 20 years from nine SEER registries during the period 1973-2003. Frequencies, age-adjusted incidence rates, annual percent change (APC) in incidence rates, and 5-year relative survival rates across three 6-year cohorts were evaluated. A total of 33,471 malignant neoplasms were identified, for an overall incidence rate of 152/1,000,000 person-years. For all cancers combined, there was a significant average annual increase (APC=0.6%; 95% Confidence Interval (CI): 0.4%-0.8%). Incidence rates increased significantly for acute lymphoblastic leukemia (0.9%), central nervous system tumors (1.1%), hepatoblastoma (2.9%), osteosarcoma (0.7%), germ cell tumors (0.9%), thyroid carcinoma (1.2%), and malignant melanoma (1.8%). Incidence rates decreased significantly for Hodgkin disease (-0.7%) and other leukemias (-3.6%). Five-year survival rates increased significantly for all histologic subtypes combined (50% in 1973-1978 to 78% in 1993-1998). The highest 5-year survival rates (1993-1998) were observed among children with retinoblastoma and thyroid carcinoma (98%) while the lowest rates were observed in children with acute myeloid leukemia (41%). Importantly, survival rates continue to improve for nearly all cancers examined. The greatest increases in survival occurred for ependymomas (+37%) and non-Hodgkin lymphoma (+35%). Our results confirm that incidence rates for pediatric cancers continue to increase over time, while survival rates are also increasing. Increasing trends in pediatric cancer incidence rates, along with the paucity of information regarding underlying causes, necessitate an ongoing need for surveillance and etiologic studies. Further, improvements in survival have produced an expanding population of childhood cancer survivors who are at risk for adverse physical and psychosocial effects and who require long-term follow-up care. Supported by NIH T32 CA099936 and the Children’s Cancer Research Fund.