tbuckley/cabot-search huggingface dataset:
68Ga PSMA PET/CT in a Rare Case of Metastatic Adenocarcinoma Prostate Presenting as Numb Chin Syndrome
Authors: Arun Sasikumar, Ajith Joy, M. R. A. Pillai, Renuka Gopal, Boben Thomas
Journal: Clinical Nuclear Medicine (2016)

A 68-year-old man presented with right-side facial numbness. MRI showed an extra-axial mass infiltrating the right temporal bone. It was debulked surgically, and histopathology revealed metastatic adenocarcinoma. Ga PSMA PET/CT done in view of increased PSA levels and clinically suspicious hard lesion in prostate showed primary lesion in left side of prostate with metastases to the right temporal bone. Primary carcinoma of the prostate and metastases to the right temporal bone were proven histopathologically. Our case highlights the usefulness of Ga PSMA PET/CT in identifying the primary site in suspected prostate cancer and mapping the metastatic sites.
Association of anaplastic oligodendroglioma and BRCA1 mutation in males: Importance of clinical reflection and counseling.
Authors: M. Frenay, F. Burel-Vandenbos, M. Met-Domestici, L. Nasca, H. Sobol, C. Lebrun
Journal: Journal of Clinical Oncology (2011)

e12001 Background: Germline mutations in BRCA1 increase the risk of breast and ovarian cancers and cancers at other sites. No specific association has been reported between BRCA1 mutation and glial tumor occurrence. Methods: A 35 year old man was diagnosed with an anaplastic oligodendroglioma after experiencing generalized seizure. Familial history reported 3 ovarian cancers. Genetic testing has been performed and shown the BRCA1 exonic deletion c.3819delGTAAA, p.1241ter. The test that has been ruled on our patient was positive too. The patient was treated with a first line chemotherapy (PCV-regimen). Brain radiotherapy (RT) was recommended but refused by the patient and a second line of CT with temozolomide began. The patient was given RT after secondary progression. Post RT MRI showed again a progression and the patient deceased 16 months after the diagnosis. Unexpectedly tumour immunohistochemistry with BRCA1 antibodies showed normal staining, thus unabling to assess the germline mutation in tumour sample. Results: Mutations in the tumor suppressor genes BRCA1 and BRCA2 are responsible for approximately 25-40% of inherited breast cancers. Mutations in the BRCA gene have not yet been associated with the development of sporadic and inherited malignant gliomas. Meanwhile breast carcinoma and glioblastoma share several genetic and molecular features which can play a role in the pathogenesis, DNA repair mechanisms and treatment sensitivity. Moreover glioblastoma can be related with several inherited disorders that also predispose towards breast cancer, including Li-Fraumeni (p53 mutation) and Cowden (PTEN mutation) syndromes. Conclusions: Genetic alterations in tumor suppressor genes, both inherited and sporadic, are involved in the carcinogenesis of many tissues. This case report points out the possible relationship between BRCA1 germline mutation and anaplastic glioma occurrence. Whereas it underlines the relevance of familial history of cancer screening not to neglect hereditary cancer susceptibility in glioma patients.
CDC Grand Rounds: Chronic Fatigue Syndrome — Advancing Research and Clinical Education
Authors: Elizabeth R. Unger, Jin-Mann Sally Lin, Dana J. Brimmer, Charles W. Lapp, Anthony L. Komaroff, Avindra Nath, Susan Laird, John Iskander
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Chronic fatigue syndrome (CFS) is a complex and serious illness that is often misunderstood. Experts have noted that the terminology "chronic fatigue syndrome" can trivialize this illness and stigmatize persons who experience its symptoms (1). The name was coined by a group of clinicians convened by CDC in the late 1980s to develop a research case definition for the illness, which, at the time, was called chronic Epstein-Barr virus syndrome. The name CFS was suggested because of the characteristic persistent fatigue experienced by all those affected and the evidence that acute or reactivated Epstein-Barr virus infection was not associated with many cases (2). However, the fatigue in this illness is striking and quite distinct from the common fatigue everyone experiences. A variety of other names have been used, including myalgic encephalomyelitis (ME), ME/CFS, chronic fatigue immune dysfunction, and most recently, systemic exertion intolerance disease (3). The lack of agreement about nomenclature need not be an impediment for advancing critically needed research and education. The term ME/CFS will be used in this article.
Abstract 1025: Protein kinase D2 promotes the proliferation of glioma cells by regulating golgi phosphoprotein 3
Authors: Xiuping Zhou, Pengfei Xue, Minglin Yang, Hengliang Shi, Dong Lu, Qiong Shi, Jinxia Hu, Rutong Yu
Journal: Cancer Research (2015)

Abstract Protein kinase D2 (PKD2) has been demonstrated to promote tumorigenesis in many types of cancers. However, how PKD2 regulates cancer cell growth is largely unknown. In this study, we found that over-expression of PKD2 promoted glioma cell growth but down-regulation of PKD2 inhibited it. Further investigation indicated that PKD2 down-regulation decreased the protein level of Golgi phosphoprotein 3(GOLPH3) as well as p-AKT level. On the contrary, over-expression of PKD2 increased the protein level of GOLPH3 and p-AKT. In addition, GOLPH3 exhibited similar effect on glioma cell growth to that of PKD2. Interestingly, GOLPH3 down-regulation partially abolished glioma cell proliferation induced by PKD2 over-expression, while over-expression of GOLPH3 also partially rescued the inhibition effect of PKD2 down-regulation on glioma cell growth. Importantly, the level of PKD2 and GOLPH3 significantly increased and was positively correlated in a cohort of glioma patients, as well as in patients from TCGA database. Taken together, these results reveal that PKD2 promotes glioma cell proliferation by regulating GOLPH3 and then AKT activation. Our findings indicate that both PKD2 and GOLPH3 play important roles in the progression of human gliomas and PKD2-GOLPH3-AKT signaling pathway might be a potential glioma therapeutic target. Citation Format: Xiuping Zhou, Pengfei Xue, Minglin Yang, Hengliang Shi, Dong Lu, Qiong Shi, Jinxia Hu, Rutong Yu. Protein kinase D2 promotes the proliferation of glioma cells by regulating golgi phosphoprotein 3. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1025. doi:10.1158/1538-7445.AM2015-1025
ACE-011, a Soluble Activin Receptor Type IIa IgG-Fc Fusion Protein, Increases Hemoglobin and Hematocrit Levels in Postmenopausal Healthy Women
Authors: Kenneth T Kim, Niels G Borgstein, Yijun Yang, Eric Haltom, Louisa Mook, Michelle D Ababa, Sandeep K Reddy, Matthew Leigh Sherman
Journal: Blood (2008)
Treatment of Thrombotic Thrombocytopenic Purpura with Heparin, Vincristine and Dexamethasone.
Authors: Jinghua Wang, Na Liu, Fang Liu, Changgeng Ruan, Juan Liu, Xi Cen, Xiaoyun Li, Haibin Dai, Bo Guo, Yanhua Su, Yanqing Zhang, Jian Zhang, Yue Guan, Hongmei Wang
Journal: Blood (2006)
3-D Ultrasound Localization Microscopy for Identifying Microvascular Morphology Features of Tumor Angiogenesis at a Resolution Beyond the Diffraction Limit of Conventional Ultrasound
Authors: Fanglue Lin, Sarah E. Shelton, David Espíndola, Juan D. Rojas, Gianmarco Pinton, Paul A. Dayton
Journal: Theranostics (2016)

Angiogenesis has been known as a hallmark of solid tumor cancers for decades, yet ultrasound has been limited in its ability to detect the microvascular changes associated with malignancy.Here, we demonstrate the potential of 'ultrasound localization microscopy' applied volumetrically in combination with quantitative analysis of microvascular morphology, as an approach to overcome this limitation.This pilot study demonstrates our ability to image complex microvascular patterns associated with tumor angiogenesis in-vivo at a resolution of tens of microns -substantially better than the diffraction limit of traditional clinical ultrasound, yet using an 8 MHz clinical ultrasound probe.Furthermore, it is observed that data from healthy and tumor-bearing tissue exhibit significant differences in microvascular pattern and density.Results suggests that with continued development of these novel technologies, ultrasound has the potential to detect biomarkers of cancer based on the microvascular 'fingerprint' of malignant angiogenesis rather than through imaging of blood flow dynamics or the tumor mass itself.
Abstract 2810: Identification of a natural compound as mammalian target of rapamycin kinase inhibitor
Authors: Jeong-Hoon Jang, Cheol-Jung Lee, Mee-Hyun Lee, Young-Joon Surh, Yong-Yeon Cho
Journal: Cancer Research (2015)

Abstract The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, plays a critical role in the regulation of Akt signaling-mediated cell proliferation and transformation. Although several synthetic chemical compounds have developed to inhibit mTOR kinase activity, only few publications have been reported on the identification of natural compounds to target the mTOR kinase active pocket. In this study, we found that AME, a natural compound, inhibited cell proliferation by impairment of G1/S cell cycle transition when cells were co-treated with tumor promoters, such as epidermal growth factor. AME directly targeted the active pocket of mTOR kinase domain by competing with adenosine triphosphate (ATP), but not with PI3K and PDK1. We further confirmed that AME inhibited phosphorylation of Akt at Ser473, which is a target amino acid of mTOR complex 2 (mTORC2), and Akt-mediated GSK3β phosphorylation at Ser9, which resulted in activation of GSK3β. The activated GSK3β inhibited cell proliferation by c-Jun phosphorylation at Ser243, which facilitated destabilization and degradation of c-Jun through an ubiquitination-mediated proteasomal degradation pathway. Notably, decreased c-Jun stability by AME treatment suppressed EGF-induced neoplastic cell transformation in JB6 Cl41 mouse skin epidermal cells and HaCaT human skin keratinocytes in soft agar assay. Taken together, these results demonstrated that AME might be a natural chemopreventive agent targeting mTOR kinase active pocket. Key words: Natural compound, ATP-competitive mTOR kinase inhibitor, mTORC2/Akt/GSK3 signaling, chemoprevention Citation Format: Jeong-Hoon Jang, Cheol-Jung Lee, Mee-Hyun Lee, Young-Joon Surh, Yong-Yeon Cho. Identification of a natural compound as mammalian target of rapamycin kinase inhibitor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2810. doi:10.1158/1538-7445.AM2015-2810
First Line Treatment with Nilotinib 800 Mg Daily Results In Unprecedentedly High Rate of Rapid, “Deep” and Stable Molecular Responses as Assessed by a High Sensitive Nanofluidic Array for the Detection of Rare Copies of BCR-ABL1 Transcript: Results of a Phase 2 Trial of the GIMEMA CML Working Party
Authors: Giovanni Martinelli, Angela Poerio, Marilina Amabile, Ilaria Iacobucci, Simona Soverini, Fausto Castagnetti, Francesca Palandri, Gabriele Gugliotta, Adele Capucci, Mario Tiribelli, Fabio Stagno, Alfonso Zaccaria, Tamara Intermesoli, Bruno Martino, Monica Bocchia, Michele Cedrone, Nicoletta Testoni, Massimo Breccia, Giuliana Alimena, Luciano Levato, Cristina Papayannidis, Annalisa Lonetti, Carolina Terragna, Domenico Russo, Fabrizio Pane, Giuseppe Saglio, Gianantonio Rosti, Michele Baccarani
Journal: Blood (2010)
Abstract 3424: The efficacy of Gasdermin gene family for tumor marker in colorectal cancer
Authors: Hajime Orita, Shigekazu Tanaka, Shunsuke Watanabe, Hirokazu Matsuzawa, Konomi Mizuguchi, Tomoaki Ito, Koji Senuma, Tomoyuki Kushida, Mutsumi Sakurada, Hiroshi Maekawa, Ryo Wada, Koichi Sato
Journal: Cancer Research (2015)

Abstract Gasdermin (GSDM/Gsdm) family was originally identified as a candidate causative gene for a mouse skin mutation, recombination induced mutation 3 (Rim3). It has four human homologs, GSDMA, GSDMB, GSDMC, and GSDMD. All GSDM family members are located in amplicons, genomic regions often amplified during cancer development, and are considered to be involved in the regulation of epithelial apoptosis. GSDMA is mainly expressed in the upper gastrointestinal tract. In contract, GSDMD is expressed in the colorectal tract. In this study, we researched those expressions in colorectal cancer and evaluated them for tumor marker, comparing between those expressions and clinical pathological status. We immunohistologically analyzed both expressions of GSDMA and GSDMD, using thirty colorectal cancer cases which were surgically treated at our institution 2013-2014 (Stage1 10 cases, Stage2 10 cases, Stage3a 10cases). Thenretrospectively analyzed the connection, between GSDM expression and clinicopathological data. GSDMA was no expressed in normal colorectal epithelium, but was overexpressed gradually rising in carcinoma. However, GSDMD showed the opposite results compared with GSDMA. The results of the expression analysis suggested that GSDMA and GSDMD act antagonictically with each other in the clinical stage of colorectal cancer. Citation Format: Hajime Orita, Shigekazu Tanaka, Shunsuke Watanabe, Hirokazu Matsuzawa, Konomi Mizuguchi, Tomoaki Ito, Koji Senuma, Tomoyuki Kushida, Mutsumi Sakurada, Hiroshi Maekawa, Ryo Wada, Koichi Sato. The efficacy of Gasdermin gene family for tumor marker in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3424. doi:10.1158/1538-7445.AM2015-3424
Deciphering of CD4+ T Cell Subsets Involved in Maintenance and Break of Immune Tolerance in a Humanized Mouse Model That Is Immune Tolerant to Human FVII
Authors: Christine Lenk, Markus Pasztorek, Markus Weiller, Rafi Uddin Ahmad, Hans Peter Schwarz, Friedrich Scheiflinger, Birgit M Reipert, Maurus de la Rosa
Journal: Blood (2011)
Prevalence of functional impairment among prostate cancer patients determined by comprehensive geriatric assessment (CGA): Baseline data for a prospective study of androgen ablation and quality of life
Authors: S. Gupta, F. Bylsma, J. Dignam, K. Kuball, W. Stadler, M. Rodin
Journal: Journal of Clinical Oncology (2004)

8210 Background: Androgen replacement has been shown to improve cognitive & physical performance in hypogonadal men. Few studies have examined the effects of total androgen blockade on cognitive & physical performance of older prostate cancer pts. We report pre-treatment performance measures of an accruing cohort of men receiving anti-androgen therapy for prostate cancer. Methods: All prostate cancer pts (≥ 50 yrs) followed at the University of Chicago, starting androgen ablation are eligible. The CGA includes self-report measures for instrumental (household IADL) and basic (self care ADL) activities of daily living. Physical performance is measured by standardized directly observed tests including Berg Balance Scale (BBS) & Timed Up and Go (TUG). Cognitive measures include the Mini-Mental Exam (MMSE) & a comprehensive neuropsychological battery (tests of attention, fine motor, executive, verbal and spatial recognition, immediate/delayed recall). All scores are normed for age, sex and education. Pts are tested within 2 weeks of first treatment with planned assessment 6 mths and 1 yr later. Results: 12 pts have completed baseline evaluations. Ages range from 57–87 (mean 71 yrs). One pt self-reported impairment with one ADL. Directly observed physical performance yielded 7 of 12 men markedly impaired at baseline balance testing (BBS score < 40 suggests high fall risk) and 3 of 12 men at risk for falls based on TUG >13 seconds. 4 of 12 men scored 22–25, (mild-moderately impaired) on MMSE. We predetermined cognitive impairment as scoring ≥ 2 SD below the mean on at least 2 different domains assessed by the neuropsychological battery. 8 of 12 men met this definition. Verbal recognition (HTLV-R) and spatial recall (Rey Complex Figure Copy) were most often impaired. Conclusions: Clinically significant impairments in cognitive & physical performance are present at baseline in our older prostate cancer pts. As androgen blockade may cause further decrements in performance, identification of men who are at increased risk for treatment-related effects is imperative. No significant financial relationships to disclose.
Are mesothelin and L1CAM useful biomarkers in primary ovarian cancer patients?
Authors: P. Wimberger, S. Kasimir-Bauer, B. Aktas, R. Kimmig, M. L. Heubner
Journal: Journal of Clinical Oncology (2011)

e15559 Background: We evaluated the impact of mesothelin, a cell surface glycoprotein and tumor differentiation antigen, and L1CAM, a cell adhesion molecule, involved in tumor progression and apoptosis in serum samples of 154 patients with first diagnosis of primary ovarian cancer. It was the purpose of the study to (a) correlate these novel biomarkers and CA12-5 levels with the presence of disseminated tumor cells (DTC) in the bone marrow (BM) and clinical parameters and (b) evaluate their prognostic value with regard to disease-free-survival (DFS) and overall survival (OS). Methods: DTC were detected in bilateral BM aspirates (10mL) using density gradient centrifugation and immunocytochemistry, applying the anti-CK antibody A45-B/B3. Serum mesothelin and L1-CAM were determined using commercial ELISA-kits (DRG). Mesothelin-positivity was defined as >2.0 nmol, L1CAM-positivity as >10 ng/mL and CA12-5 elevation as >35 U/mL, respectively. Results: 22/154 (14%) patients were platinum-resistent with a significantly decreased mean OS of 27.3 months (95%CI: 18.9-35.6) versus 54.8 months (95%CI: 48.6-61.0) in platinum-sensitive patients. Mesothelin-positivity (present in 37.9%) significantly correlated with advanced FIGO stages (p=0.002), residual tumor (p<0.0001), serous histological subtype (p<0.0001) and higher age (p<0.000). In contrast, L1CAM-positivity (in 7.8%) showed no correlation with any of these parameters. Elevated CA12-5 levels (in 88.1%) significantly correlated with advanced stages (p<0.0001), residual tumor (p=0.046), serous histological subtype (p<0.0001) and age (p=0.018). DFS and OS were significantly decreased in case of mesothelin-positivity and CA12-5 elevation, but not for L1CAM-positive cases. DFS was 25.1 months (95%CI: 17.9-32.3) in mesothelin-positive patients versus 47.2 months (95%CI: 39.3-55.0) in mesothelin-negative patients (p=0.004). Corresponding data for OS were 36.1 months (95%CI: 28.1-44.1) in case of mesothelin-positivity versus 57.7 months (95%CI: 50.8-64.6) in mesothelin-negative cases (p=0.001). Conclusions: Mesothelin seems to be a useful biomarker for therapy monitoring and could be an attractive target for cancer therapy in ovarian cancer patients.
Formation of Nitroso Compounds in the Reaction of Nitrite and Hemoglobin.
Authors: Swati Basu, Jinming Huang, Zhi Huang, Anne Jeffers, Alice Jiang, Xiaojun He, Ivan Azarov, Ryan Seibert, Rakesh P. Patel, Neil Hogg, Bruce King, Mark T. Gladwin, Daniel Kim-Shapiro
Journal: Blood (2006)
Identifying Inherited and Acquired Genetic Factors Involved in Poor Stem Cell Mobilization and Donor-Derived Malignancy
Authors: Katarzyna Rojek, Eric Nickels, Barbara Niestadt, Rafael Marquez, Amittha Wickrema, Andrew Artz, Koen van Besien, Ming K Lee, Jeremy P. Segal, Mary-Claire King, Tom Walsh, Akiko Shimamura, Sioban Keel, Jane E Churpek, Lucy A Godley
Journal: Blood (2015)
371. AAV-Based Gene Therapy in a Mouse Model of Smith Lemli Opitz Syndrome (SLOS)
Authors: Saloni Y. Pasta, Flora Ting, Dorothy Tabron, Sean Sun, Saurin Kadakia, Cedric Shackleton, Gordon Watson
Journal: Molecular Therapy (2015)

We are using AAV-based gene therapy to restore cholesterol biosynthesis in a mouse model for Smith Lemli Opitz syndrome (SLOS). Mutations in the 7-dehydrocholesterol reductase gene (DHCR7) are responsible for this inborn error resulting in cholesterol deficiency and accumulation of potentially toxic 7-and 8-dehydrocholesterol (DHC) precursors. The central nervous system (CNS) is significantly impacted in affected individuals; present forms of therapy by dietary cholesterol supplementation fail to restore cholesterol homeostasis in these tissues due to the blood brain barrier (BBB). Previously, we showed that intravenous gene therapy using AAV vectors had a positive effect on systemic cholesterol homeostasis, but that cholesterol metabolism in the CNS was unaffected. To target the CNS and bypass the restrictive BBB, an AAV2/8 vector carrying a normal copy of the human DHCR7 gene was introduced into the cerebrospinal fluid via intrathecal injection. Three-day-old SLOS mice (compound heterozygotes containing a null allele and a hypomorphic allele of Dhcr7) were treated and 8 weeks later various nervous and non-nervous tissues were analyzed for sterols by gas chromatography and mass spectrometry. Resulting data were expressed as the DHC/cholesterol ratio, an index of SLOS biochemical severity. In addition the presence of the rescue gene and expression of its mRNA in the CNS were evaluated by real-time quantitative PCR. We observed partial normalization of the DHC/cholesterol ratio in the brain and spinal cord of treated mice. A similar effect was also noted in the sciatic nerves, which form part of the peripheral nervous system. In contrast, sterol levels in the liver, which received little or no vector, were not significantly affected. In brain the extent of improvement in the DHC/cholesterol ratio correlated with the level of vector DNA and the level of human DHCR7 mRNA expression indicating a dose/response relationship. The effect of neonatal vector administration was sustained into adulthood, to at least 8 weeks of age. Thus, vector and its expression persisted through the postnatal period of dramatic growth and tissue expansion. These results demonstrate the first potential means of treating the nervous system in SLOS patients. We suggest that providing treatment early in nervous system development could minimize and possibly to some extent even reverse the effects of inherited cholesterol deficiency. Used in combination with systemic gene delivery, this means of treatment may result in providing (the most) effective overall treatment for this debilitating disorder.