tbuckley/cabot-search huggingface dataset:
Combination of GnRH analogue and aromatase inhibitor as an adjuvant therapy in premenopausal nonmetastatic breast cancer.
Authors: O. Modiramani, N. Najafizadehgan, F. Elahi
Journal: Journal of Clinical Oncology (2011)

e11022 Background: Adjuvant hormonal therapy has been shown to decrease the risk of breast cancer recurrence and overall mortality in premenopausal nonmetastatic breast cancer patients and can be accomplished by ovarian suppression or ablation, tamoxifen, or combined ovarian suppression/ablation plus tamoxifen. ongoing clinical trials for benefits & efficacy of aromatase inhibitors combined with ovarian suppression in these patients are initiated. Methods: Phase II clinical trial (2001-2010) was performed in premenopausal histologically proved hormone positive breast cancer patients with intermediate or high adverse risks receiving adjuvant triptorelin (3.75mg every 28 days) + aromatase inhibitor [letrozole (2.5 mg daily) or exemestane (25mg daily)] + biphosphonate after local and/or systemic therapy. Results: 204 female patients were enrolled. Mean age 42.1 (18-54 yr), tumor size (T1: 29.4%, T2: 58.8%, T3: 11.8%, T4: 2.5%), Mean Involved lymph nodes 2.28(0-26), Grade (I 13%, II 59.3%, III 26.5%) Her2/neu + 18.1% Lymphovascular invasion 20%, Surgery (56.9% MRM 43.1% BCT), chemotherapy (doxorubicin hydrochloride-taxan based 91.7% and non Taxan based 8.3%) Radiotherapy (88.2%). After Median 37 months follow up (3 – 116 mon), Tumor Recurrence (Bone, Liver and Pleura) was seen in 4 patients (1.96%), 43, 48, 67 and 98 months after beginning of hormone therapy. One of them was died of tumor complication (recurrence after 48 and death 66 months of hormontherapy). Mortality rate 0.5%; 95% CI: 0.01-2.7% and relapse rate 1.96%; 95% CI: 0.54-4.94%) patients with Tumor Recurrence are >=39 yr (p<0.355), 75%T2 and 25% T3(p<0.114), 50% her2/neu+(p<0.097), grade II 50% and Grade III 25% (p<0.728) 75%BCT surgery (p<0.199) and 50% lymphovascular invasion (p<0.135). The number of involved lymph nodes are strong predictor of recurrence (p<0.005). 5 patients with inflammatory breast cancer were treated in this study who did not have tumor recurrence after mean 75 months follow up. Conclusions: It seems that combination of GnRH analogue and aromatase inhibitor is an effective and tolerable adjuvant hormonal therapy.
PAX5-PML Induces Pro B Acute Lymphoblastic Leukemia in Mice
Authors: Naoto Imoto, Shingo Kurahashi, Fumihiko Hayakawa, Takahiko Yasuda, Keiki Sugimoto, Yuki Kojima, Takanobu Morishita, Yuichiro Inagaki, Shinobu Tsuzuki, Tomoki Naoe, Hitoshi Kiyoi
Journal: Blood (2014)
A Possible Role for Wnt3a in Enhancing StemRegenin1-Mediated Expansion of Hematopoietic Stem Cells
Authors: Lucia Duinhouwer, Elwin Rombouts, Nesrin Tüysüz, Jan Spanholtz, Derk ten Berge, Dirk Groenewegen, Eric Braakman, Jan Cornelissen
Journal: Blood (2012)
Abstract 1222: p53 downregulates CRKL proto-oncogene protein through miR-200 family
Authors: Yasushi Sasaki, Miyuki Tamura, Kenta Kobashi, Kousuke Takeda, Takafumi Nakagaki, Masashi Idogawa, Takashi Tokino
Journal: Cancer Research (2015)

Abstract The downregulation of the miR-200 family has been involved in the progression and metastasis of human cancers. The miR-200 family includes two clusters: miR-200b, miR-200a and miR-429 (miR-200b-200a-429) located on chromosome 1; and miR-200c and miR-141 (miR-200c-141) located on chromosome 12. We identified response elements located around both clusters that are responsive to p53 family. Based on the similarity of their seed sequences, miR-200b, miR-200c and miR-429 have identical seed sequences, whereas the seed sequence of miR-141 and miR-200a is similar, but not identical, suggesting that miR-200b, miR-200c and miR-429 share similar mRNAs target. Here, in silico miRNA target prediction identified the v-crk sarcoma virus CT10 oncogene homolog-like (CRKL) as a potential target for miR-200b, miR-200c and miR-429 (miR-200b/200c/429). miR-200b/200c/429 inhibits the expression of CRKL mRNA and protein by directly targeting its 3′-UTR region. Importantly, endogenous CRKL expression was decreased in cancer cells with introduction of wild-type p53 and TAp63γ. Oncomine database shows that CRKL levels are significantly overexpressed in multiple cancer types compared with the corresponding normal tissues. We also found that CRKL was overexpressed in primary breast cancer tissues harboring mutant p53 genes. Our results indicate that miR-200b/200c/429, a p53-inducible miRNA, is a negative regulator of the CRKL oncoprotein and suggest a new p53-miR-200-CRKL pathway in carcinogenesis. Citation Format: Yasushi Sasaki, Miyuki Tamura, Kenta Kobashi, Kousuke Takeda, Takafumi Nakagaki, Masashi Idogawa, Takashi Tokino. p53 downregulates CRKL proto-oncogene protein through miR-200 family. [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 1222. doi:10.1158/1538-7445.AM2015-1222
Maintenance Therapy with Bortezomib Plus Thalidomide (VT) or Bortezomib Plus Prednisone (VP) In Elderly Myeloma Patients Included In the GEM2005MAS65 Spanish Randomized Trial
Authors: María-Victoria Mateos, Albert Oriol, Ana-Isabel Teruel, Enrique Bengoechea, Montse Pérez, Javier López, Joaquín Díaz-Mediavilla, Jose Mariano Hernández, Felipe de Arriba, Yolanda Gonzalez, Joan Bladé, Juan José Lahuerta, JesÃ°s F. San Miguel
Journal: Blood (2011)
Unsuspected Metastatic Ovarian Cancer Revealed by 18F-NaF PET/CT Performed to Evaluate Lower-Back Pain
Authors: Yan Zhu, Yue Chen, Zhanwen Huang, Lan Liu
Journal: Clinical Nuclear Medicine (2016)

A 59-year-old woman with back pain underwent an F-NaF PET/CT bone scan. Unexpectedly, multiple foci of increased tracer uptake were present in the abdomen and pelvis, which corresponded to the calcified soft tissue masses. The subsequent F-FDG PET/CT not only confirmed increased FDG activity in these partially calcified mass but also revealed abnormal activity in noncalcified lesions. The pathological examination demonstrated that the patient had ovarian cancer.
Disease-Related Symptoms Reported across a Broad Population of Patients with Paroxysmal Nocturnal Hemoglobinuria.
Authors: Gabrielle Meyers, Ilene Weitz, Thierry Lamy, Jean-Yves Cahn, Henk-André Kroon, Beth Severino, Maria Teresa Uranga, Miguel Sanz Alonso, José Antonio García Vela, Anita Hill
Journal: Blood (2007)
Abstract 1585: Application of a graphene oxide based microfluidic device (GO Chip) to prostate cancer circulating tumor cell capture and analysis
Authors: Molly Kozminsky, Hyeun Joong Yoon, Nallasivam Palanisamy, Kathleen Cooney, Maha Hussain, Ajjai Alva, Todd Morgan, Sunitha Nagrath
Journal: Cancer Research (2015)

Abstract One in seven men in the United States will be diagnosed with prostate cancer in his life time, in part because of the prevalence of screening for serum levels of prostate specific antigen (PSA). However, this has led to the overtreatment of the disease, leading to recommendations against frequent PSA testing and establishing the need for a more informative biomarker in prostate cancer. Circulating tumor cells (CTCs) are rare cells present in the blood stream of cancer patients at the low frequency on the order of one CTC in one billion normal blood cells. The graphene oxide chip (GO Chip) is a microfluidic CTC capture device with increased sensitivity and purity due to its use of the nanomaterial graphene oxide to present a capture antibody against the epithelial cellular adhesion molecule (EpCAM). In this study, whole blood was collected from 50 prostate cancer patients, including those with metastatic, localized, castrate resistant, and castrate sensitive disease, and analyzed using the GO Chip. Captured cells were stained for cytokeratin, CD45, and DAPI, with nucleated cytokeratin positive cells being denoted as CTCs. CTCs were detected in 47 out of 50 patients, and an average of 5.94 CTCs/mL was recovered from each sample. Correlation of CTCs with surrogate endpoints could improve the utility of CTCs as a liquid biopsy, potentially advancing their application in translational research. Citation Format: Molly Kozminsky, Hyeun Joong Yoon, Nallasivam Palanisamy, Kathleen Cooney, Maha Hussain, Ajjai Alva, Todd Morgan, Sunitha Nagrath. Application of a graphene oxide based microfluidic device (GO Chip) to prostate cancer circulating tumor cell capture and analysis. [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 1585. doi:10.1158/1538-7445.AM2015-1585
A dose confirmation and signal-generating study of the immunocytokine L19-IL2 in combination with dacarbazine in patients with metastatic melanoma.
Authors: T. K. Eigentler, B. Weide, G. Spitaleri, F. G. De Braud, A. Romanini, R. Gonzales-Inglesias, A. Tasciotti, L. Giovannoni, K. Schwager, V. Lovato, M. Kaspar, E. Trachsel, D. Neri, H. D. Menssen, C. Garbe
Journal: Journal of Clinical Oncology (2011)

2531 Background: L19-IL2 is a tumor-targeting immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a marker of tumor angiogenesis, and of human interleukin-2 (IL2). L19-IL2 is able to selectively deliver IL2 to tumor tissues exploiting the expression of EDB on newly formed blood vessels. The recommended monotherapy dose (RD) of 22.5 MioIU IL2 equivalents (day 1, 3, and 5) of L19-IL2 was defined earlier. In this study, we investigated L19-IL2 in combination with dacarbazine in patients with metastatic melanoma, assessing safety, tolerability, and activity. Methods: The study consists of a dose confirmation part, during which 10 patients with metastatic melanoma were enrolled, followed by a fixed dose part, during which 22 chemo-naive metastatic melanoma patients were treated at the RD. Patients received intravenous infusions of L19-IL2 (10, 15 and 22.5 MioIU during dose confirmation, and 22.5 MioIU in the fixed dose part of the study) on day 1, 3 and 5 in combination with 1 g/m2 of dacarbazine on day 1, every 21 days. Up to 6 treatment cycles were given, followed by a maintenance phase during which only L19-IL2 was applied biweekly. Tumor assessment was performed every 6 weeks. Data on safety and efficacy were evaluated using CTC v3.0 and RECIST criteria, respectively. Results: Median age was 55 years (30-83). The RD was confirmed to be 22.5 MioIU. Toxicity was manageable and reversible, with no treatment related deaths. Twenty-nine out of 32 patients were evaluable for efficacy according to RECIST. In a centralized radiology analysis, 8/29 patients achieved RECIST-confirmed objective responses, including a complete response, still ongoing 21 months after start of treatment. The one-year survival rate was 61.5% and median overall survival was 14.4 months for all patients treated at RD. Conclusions: L19-IL2 combined with dacarbazine, both at RD, can be safely and repeatedly administered to patients with metastatic melanoma, and showed promising signs of clinical activity. To further evaluate this combination therapy for metastatic melanoma, a controlled randomized phase II trial is ongoing.
Abstract 1712: CAMKV as an immunotherapy target in MYCN-amplified neuroblastoma
Authors: Robyn T. Sussman, Kevin Huang, Pichai Raman, John M. Maris
Journal: Cancer Research (2015)

Abstract Background: Neuroblastoma is an embryonal tumor of the developing sympathetic nervous system that accounts for 10-15% of pediatric cancer-related deaths. Although an intensive treatment regimen consisting of chemotherapy, surgery, radiation, immunotherapy and autologous stem cell transplant is used for patients with high-risk neuroblastoma, about half of these patients ultimately die. Reliable tumor-specific genomic biomarkers, such as MYCN amplification, have been identified for high-risk neuroblastoma and are used to stratify therapy. Recent clinical studies using immunotherapies to target cell surface molecules such as GD2 in neuroblastoma and CD19 in leukemia have shown impressive results, and have highlighted immunotherapy as a critical strategy in combating childhood cancer. Methods: As part of the Stand Up 2 Cancer/St. Baldrick's Pediatric Cancer Dream Team's effort to streamline new immunotherapuetics into the clinic, we developed a computation approach to prioritize new targets for immunotherapy for high-risk neuroblastoma. Here we used MYCN as a biomarker for the most aggressive subset of neuroblastoma to define candidate cell-surface targets that are differentially expressed in MYCN-amplified neuroblastoma. We used RNAi to manipulate gene expression levels of MYCN to determine if these cell-surface targets are under the control of MYCN in neuroblastoma cells. Results: The most significant differentially expressed cell surface molecule in high-risk neuroblastoma based on MYCN-amplification status was the calmodulin kinase-like vesicle-associated gene (CAMKV, p = 1×10-6), which encodes a protein that binds calmodulin in the presence of calcium, but lacks the kinase activity of other calmodulin kinase family members. We have confirmed that CAMKV protein is selectively expressed in MYCN-amplified neuroblastoma cell lines. From membrane fractionation and immunohistochemistry, we have verified that CAMKV is membranous in MYCN-amplified neuroblastoma cell lines and xeongraft tumors. Immunohistochemistry also revealed that CAMKV is not highly expressed in human pediatric normal tissues with the exception of neural tissues. Depletion of MYCN using RNAi resulted in a significant reduction in CAMKV RNA and protein expression (p = 2.3×10-6). Conclusions: These results provide a template for the discovery and validation of immunotherapeutic targets in MYCN-amplified neuroblastoma and have the potential to lead to the development of a new immunotherapy targeting CAMKV. Citation Format: Robyn T. Sussman, Kevin Huang, Pichai Raman, John M. Maris. CAMKV as an immunotherapy target in MYCN-amplified neuroblastoma. [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 1712. doi:10.1158/1538-7445.AM2015-1712
Factor VIIa-CTP, a Novel Long-Acting Coagulation Factor, Displays a Prolonged Hemostatic Effect and Augmented Pharmacokinetics and pharmacodynamics Following IV and SC Administration in Hemophilic Animal Models
Authors: Gili Hart, Oren Hershkovitz, Ahuva Bar-Ilan, Uri Seligsohn, Eyal Fima
Journal: Blood (2012)
Targets to reduce malaria unlikely to be met, says WHO
Authors: Sophie Cousins
Journal: BMJ (2016)

The number of pregnant women in sub-Saharan Africa receiving intermittent preventive malaria treatment (ITPp) increased fivefold between 2010 and 2015, according to the World Health Organization’s (WHO) World Malaria Report 2016.1 But targets set in 2015 to reduce the burden of malaria are unlikely to be met at the current rate of interventions, an author of the report has said.

Last year, ITPp coverage across 20 countries in the region reached 31%, up from 6% in 2010. This intervention reduces maternal malaria episodes, maternal and fetal anaemia, placental parasitaemia, low birth weight, and …
Abstract 2588: Anti-tumor effect of afatinib, an irreversible EGFR/HER2 dual inhibitor, in lung cancers harboring HER2 oncogene
Authors: Ken Suzawa, Shinichi Toyooka, Masakiyo Sakaguchi, Tomoaki Ohtsuka, Mototsugu Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi
Journal: Cancer Research (2015)

Abstract HER2 is a member of the EGFR family of tyrosine kinase receptors and plays important roles in the pathogenesis of certain human cancers. In non-small cell lung cancer (NSCLC), HER2 amplification or mutations are reported. However, little is known about the benefit of HER2-targeted therapy for NSCLC harboring HER2 alteration. In this study, we investigated the anti-tumor effect of afatinib, an irreversible EGFR/HER2 dual inhibitor, in lung cancers harboring HER2 oncogene alteration, including the novel HER2 mutations in transmembrane domain which we recently identified. Ectopically overexpressing HER2 wild-type or mutant (G776V,Cins, A775insYVMA, G660D, and V659E) in normal bronchial epithelial cells, BEAS2B, showed constitutive autophosphorylation of HER2 and activation of downstream signaling. They were sensitive to afatinib, but insensitive to EGFR-TKI (gefitinib). Furthermore, we examined anti-tumor activity of afatinib and gefitinib in several NSCLC cell lines, and investigated the association between their genetic alteration and sensitivity to afatinib treatment. Afatinib down-regulated the phosphorylation of HER2, EGFR, and their downstream signalings, and induced anti-proliferative effect through a G1 arrest and apoptotic cell death in HER2 altered cells (H2170, Calu-3, and H1781). Whereas, HER2 non-dependent NSCLC cells (A549, H1299, and H1993) were insensitive to afatinib. Our results strongly suggest that afatinib is a therapeutic option for NSCLC patients with HER2 alteration. Citation Format: Ken Suzawa, Shinichi Toyooka, Masakiyo Sakaguchi, Tomoaki Ohtsuka, Mototsugu Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi. Anti-tumor effect of afatinib, an irreversible EGFR/HER2 dual inhibitor, in lung cancers harboring HER2 oncogene. [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 2588. doi:10.1158/1538-7445.AM2015-2588
Abstract 4546: Depleting cysteine: A novel approach to tumor therapy
Authors: Marie H. Hanigan, Anthony W. G. Burgett, Nancy Wakeham, Simon S. Terzyan
Journal: Cancer Research (2015)

Abstract A cure remains elusive for many types of tumors that initially respond to chemotherapy but recur with drug-resistant disease. Cysteine, (or its oxidized form cystine) is an essential amino acid for tumors. Enhanced uptake of cysteine and/or cystine is required for tumors to maintain their intracellular glutathione (GSH) levels and redox balance. In addition, some stem cells within epithelial tumors express CD44v8-10, which stabilizes the cystine transporter, increasing cystine uptake into the cell and enhancing resistance to pro-oxidant therapy. Depleting cysteine during treatment has a profound effect on sensitizing the tumor to therapy. We have a novel strategy that reduces the cysteine (and cystine) concentration in serum and extracellular fluid. The strategy exploits the finding that a severe cysteine deficiency develops in mice lacking the enzyme gamma-glutamyl transpeptidase (GGT). This enzyme reclaims the cysteine from GSH as the blood is filtered through the kidney. Inhibiting GGT activity results in excretion of GSH in the urine and a precipitous drop in the concentration of cysteine and cystine in serum. The inhibitors of GGT that have been evaluated in the clinic are glutamate analogs and are too toxic for clinical use. We have discovered and are developing a new class of GGT inhibitors that are not glutamate analogs. These inhibitors are orders of magnitude less toxic than the glutamate analogs. We have determined the crystal structure of human GGT. In the current study we have co-crystallized human GGT with a series of inhibitors. We report the identification of residues within the active site that are critical for inhibitor binding. We have identified changes in the conformation of the active site upon substrate binding. We have also delineated movement within the active site during substrate cleavage. Site-directed mutagenesis and functional assays have confirmed the role of the key residues identified in the structural studies. These data provide new insights for continued development of a potent, specific, non-toxic inhibitor of GGT that can be used clinically in cancer therapy. Supported by an Institutional Development Award (IDeA) from the National Institutes of Health under grant P20GM103640. Citation Format: Marie H. Hanigan, Anthony W. G. Burgett, Nancy Wakeham, Simon S. Terzyan. Depleting cysteine: A novel approach to tumor therapy. [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 4546. doi:10.1158/1538-7445.AM2015-4546
Altered Expression and Signalling of Bone Morphogenetic Protein Receptor 1A (BMPR-1A) and Enhanced Hematopoietic Progenitor Cell Growth in Long-Term Stromal Culture Assays from Two Patients with a Myeloproliferative Syndrome and Pulmonary Hypertension.
Authors: Martin Hildebrandt, Kurt Bommert, Kirstin Rautenberg, Wolf-Dieter Ludwig
Journal: Blood (2006)
Who could be appropriate candidates for partial nephrectomy in localized renal cell carcinoma? Selection by preoperative factors.
Authors: Kazuhiro Nagao, Shigeru Sakano, Nakanori Fujii, Keita Kobayashi, Ryo Inoue, Yoshiaki Yamamoto, Hiroaki Matsumoto, Hideyasu Matsuyama
Journal: Journal of Clinical Oncology (2016)

542 Background: Chronic kidney disease (CKD) is a risk factor for the cardiovascular disease, which affect to the patients’ survival, while an EORTC randomized control trial did not show superiority of partial nephrectomy (PN) against localized renal cell carcinoma (RCC) in overall survival compared to radical nephrectomy (RN). We aimed to evaluate the role of operative methods affecting the survival and tried to estimate a predictive model for high risk CKD after surgery. Methods: We reviewed the data of 357 cases with clinical T1 RCC treated by RN (292 cases, RN group) or PN (65 cases, PN group) at Yamaguchi University Hospital or its related hospitals. We supposed the cases with CKD stage 3b or higher after surgery as high risk CKD. And we set the primary endpoints as the ratio of the cases with high risk CKD and overall survival after surgery. Results: Median follow-up period after surgery was 70 months (3-161). Statistically significant difference in performance status and clinical T stage were observed between the groups, but not in other patients’ characteristics. Mean values of preoperative eGFR were 69.2 and 65.5 ml/min/1.73m 2 in RN and PN group, which decreased to 46.0 and 57.9 at 5 years after surgery, respectively. There was a significant difference in the incidence of high risk CKD between RN (39.3%) and PN group (2.2%) at 5 years after surgery. During follow up period, 17 cases (4.4%) were inducted to dialysis, there was no difference in the incidence between the RN and PN group. Multivariate analysis showed that eGFR ( &lt; 72 ml/min/1.73m 2 ; Odds ratio 15.3), proteinuria (Odds ratio 3.84), smoking (Odds ratio 2.76), BMI ( &gt; 23; Odds ratio 2.66) and age ( &gt; 67 years old; Odds ratio 2.47) could be significant predictive factors for high risk CKD at 5years after surgery. Our predicting model for high risk CKD showed 86.8% of sensitivity and 74.8% of specificity. But there was no significant difference in overall survival between the RN and PN group. Conclusions: Although there was a significant difference in the incidence of high risk CKD between RN and PN group, operative methods did not affect to the survival. Postoperative high risk CKD could be predictable by preoperative clinical factors.
Molecular Long-Term Surveillance of CML Patients on Imatinib Therapy. Follow-Up of German Patients Treated within the IRIS Trial.
Authors: Martin C. Mueller, P. Paschka, T. Lahaye, Ch. Lorentz, N. Gattermann, D. Niederwieser, G. Ehninger, St Fruehauf, A. Neubauer, Th. Fischer, B. Schultheis, S. Kreil, U. Haus, R. Hehlmann, A. Hochhaus
Journal: Blood (2004)