tbuckley/cabot-search huggingface dataset:
Combination chemotherapy of intraperitoneal carboplatin and intravenous taxane in advanced endometrial cancer: A pilot study
Authors: S. Nagao, R. Oishi, Y. Tsukamoto, Y. Nakanishi, N. Iwasa, M. Shimizu, T. Goto, K. Fujiwara
Journal: Journal of Clinical Oncology (2008)

16560 Background: This is a pilot study to assess the efficacy and safety of combination chemotherapy of intraperitoneal (IP) carboplatin and intravenous (IV) taxane (paclitaxel or docetaxel) in advanced endometrial cancer for the future trial. Methods: The patients eligible for this study had histologically confirmed endometrial cancer with peritoneal carcinomatosis and/or positive for peritoneal cytology. A Bard IP port system was placed within the subcutaneous fat when the primary surgery was underwent. IV Paclitaxel 175 mg/m2 or IV docetaxel 60 mg/m2 was administered followed by IP carboplatin administration based on an area under the curve 6. Chemotherapy was repeated every 3 weeks for at least 3 courses depending on the purpose of the therapy. The toxicity grade was determined by National Cancer Institute common toxicity criteria version 2. Results: During April 2000 and March 2005, 13 patients were entered in this study. The distribution of stage was IIIA, 7; IIIB, 1; IIIC, 3; IVB, 2. There were 5 endometrioid adenocarcinoma grade 1, 7 endometrioid adenocarcinoma grade 2 and 1 endometrioid adenocarcinoma grade 3. Seven patients received IP carboplatin with IV paclitaxel and 6 patients received IP carboplatin with IV docetaxel. The incidences of grade 3/4 toxicities were 77% for neutrocytopenia, 23% for thrombocytopenia, and 15% for anemia. No grade 3/4 non-hematological toxicity was observed. No patient encountered catheter problems. Median follow up period was 61 months. Two patients with stage IVB and 2 patients with stage IIIC recurred and died of disease. No patient with stage IIIA recurred. Conclusions: The combination of IP carboplatin and IV taxane is an effective and safe for advanced endometrial cancer. Further evaluation particularly targeted on stage IIIA endometrial carcinoma is warranted. No significant financial relationships to disclose.
Prognostic Impact of DNA Repair and MDR-1 Gene Polymorphisms In De Novo Acute Myeloid Leukemia with t(8;21) or Inv(16)
Authors: Yeo-Kyeoung Kim, Soo-Young Bae, Hee Nam Kim, Nan Young Kim, Hee-Je Kim, Soo-Mee Bang, Deog-Yeon Jo, Jong-Ho Won, Na-Ri Lee, Jae-Yong Kwak, Jae-Sook Ahn, Deok-Hwan Yang, Il-Kwon Lee, Je-Jung Lee, Hyeoung Joon Kim
Journal: Blood (2010)
Case 79-1962
Authors: Jacob Lerman, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of CaseA sixty-four-year-old man was admitted to the hospital because of sudden collapse.On the day of admission the patient abruptly fell to the right and collapsed, but did not lose consciousness. He was unable to speak, respond to commands or execute purposeful movements, although he could move the left arm and leg. He had not had a headache, and there was no history of syncope, dizziness, weakness or visual disturbance.Five months before entry he experienced an episode of palpitation, dyspnea and cyanosis that was successfully treated with carotid-sinus massage, imipramine hydrochloride (Tofranil) and phenobarbital; at that . . .
Abstract 3403: Amphiregulin promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma cells
Authors: Yu-Wen Huang, Hsiao-Chi Tsai, Chih-Hsin Tang
Journal: Cancer Research (2016)

Abstract Chondrosarcoma is the second most common sarcoma in bone malignancy and is characterized by a high metastatic potential. Angiogenesis has been considered an important role in the cancer metastasis. Therefore, a better understanding of angiogenic and metastatic pathways are needed. Amphiregulin (AR) has been implicated in tumor metastasis and angiogenesis. However, the relationship of amphiregulin with vascular endothelial growth factor A (VEGF-A) expression and angiogenesis in human chondrosarcoma cells is mostly unknown. In this study, we found that the expression of amphiregulin and VEGF-A were correlated with tumor stage and were significantly higher than that in the normal cartilage. VEGF-A expression increased which depend on time and dose dependent of amphiregulin. Exogenous amphiregulin with chondrosarcoma cells promoted VEGF-A expression and subsequently increased migration, proliferation and tube formation in endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs). We also found that amphiregulin increased VEGF-A expression and angiogenesis through focal adhesion kinase (FAK), Src and protein kinase C (PKC) signaling pathway. Knockdown of amphiregulin decreased VEGF-A expression in chondrosarcoma cells. The angiogenesis effects in Matrigel plug nude mice model in vivo was also abolished in amphiregulin-knockdown cells. Taken together, these results indicate that amphiregulin occurs through FAK, Src, and PKC pathway, resulting in the activation of VEGF-A expression and contributing to the angiogenesis of human chondrosarcoma cells. Citation Format: Yu-Wen Huang, Hsiao-Chi Tsai, Chih-Hsin Tang. Amphiregulin promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3403.
Case 19-1963
Authors: Edward P. Richardson, Benjamin Castleman, Raymond D. Adams
Journal: New England Journal of Medicine (1963)

Presentation of CaseA twenty-five-year-old man was brought to the hospital in coma.Four months before admission the patient was admitted to another hospital because of increasingly severe soreness of the eyes, fatigue, double vision and numbness of the left side of the face and the left hand. Neurologic examination demonstrated leftmedial-rectus weakness on lateral gaze, coarse horizontal nystagmus on right lateral gaze, vertical nystagmus on upward gaze, a left scotoma for red and white objects, mild left hyper-reflexia and a left extensor plantar response. Examination of the cerebrospinal fluid was negative. After discharge the diplopia persisted, and there were . . .
New investigational drugs with single-agent activity in multiple myeloma
Authors: A M Rajan, S Kumar
Journal: Blood Cancer Journal (2016)

Abstract The treatment of multiple myeloma (MM) is rapidly evolving. In the United States, four drugs (panobinostat, ixazomib, daratumumab and elotuzumab) were approved for the treatment of MM in 2015. As a result of improved diagnosis and therapy, there has been a dramatic improvement in the outcome of MM in the last decade, probably more than any other malignancy. Numerous agents continue to be studied in preclinical models and in clinical trials, with many demonstrating clinical efficacy that appears promising enough to have a trajectory for regulatory approval. The purpose of this article is to summarize the current data and provide perspective on new investigational agents with promising single-agent activity in MM. The agents reviewed include Isatuximab, an anti-CD38 monoclonal antibody; marizomib, a new proteasome inhibitor; oprozomib, an oral proteasome inhibitor; filanesib (ARRY-520), a kinesin spindle protein inhibitor; dinaciclib, a cyclin-dependent kinase inhibitor; venetoclax (ABT-199), a selective BCL-2 inhibitor; and LGH-447, pan PIM kinase inhibitor.
Abstract 4062: Human mammary tumor virus (HMTV) is a breast cancer pathogen
Authors: James F. Holland, Stella Melana, Teiko Nartey, Joseph Tripodi, Shabnam Jaffer, Anupna Nayak, Beatriz GT Pogo
Journal: Cancer Research (2016)

Abstract Human mammary tumor virus (HMTV) a betaretrovirus 90-98% homologous to Mouse Mammary Tumor Virus (MMTV), the causative agent for breast cancer in mice, has been detected in approximately 40% of American women's breast cancers. Mouse DNA contamination has been definitively excluded by contamination-free guarantee techniques. In Western European countries and their former colonies, age standardized rates (ASR) of breast cancer incidence (47 to 92 per 100,000 per year) are higher than Asian incidence (29 to 43 ASR/y). This difference could be explained by excess HMTV-related breast cancer incidence. In 7 West European, American and Oceania countries, 30 to 60% contain HMTV, while in 5 Asian nations HMTV associated breast cancers range from 0 to 22%. Different indigenous murine species with disparate MMTV burdens parallel these findings: mus domesticus in the West with much MMTV in its genome, and mus castaneus or mus musculus in the East with less. HMTV is found in cells in milk of 8% of unselected American mothers and in milks of 21% of women previously biopsied for unconfirmed cancer suspicion. HMTV isolated from primary cultures of metastatic breast cells is able to infect In vitro, human mammary epithelial cells, B and T lymphocytes and dendritic cells. MCF10A breast cell line infected with HMTV shows molecular changes associated with epithelial-mesenchymal transition, such as up-regulation of vimentin, and down-regulation of E-cadherin. HMTV sequences were also shown to be more prevalent in inflammatory, gestational and familial breast cancers than in unselected sporadic samples, consistent with association with more aggressive breast cancer phenotypes. To establish a direct connection between the presence of HMTV sequences and metastatic breast cancer, we have found HMTV sequences in 94% of primary cultures of metastatic breast cells obtained directly from effusion fluids. HMTV present in primary breast tumors has been demonstrated in their metastatic axillary nodes. Taken together the results suggest an association between the presence of HMTV sequences and breast cancer aggressiveness. HMTV poses a new and challenging dimension in breast cancer research involving causation, diagnosis, molecular mechanisms, epidemiology, therapy and prevention. Citation Format: James F. Holland, Stella Melana, Teiko Nartey, Joseph Tripodi, Shabnam Jaffer, Anupna Nayak, Beatriz GT Pogo. Human mammary tumor virus (HMTV) is a breast cancer pathogen. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4062.
Abstract 267: Preclinical investigation of the HSP90 inhibitor, ganetespib, in combination with FDA-approved cytotoxic agents for their potential anti-tumor effects on human neuroendocrine tumors
Authors: Chung Wong, Evan Vosburgh, Arnold Levine, David Proia, Eugenia Xu
Journal: Cancer Research (2016)

Abstract The gastroenteropancreatic neuroendocrine tumor (GEP-NET) system is comprised of a heterogeneous group of tumors with increasing incidence. Current standard of care cytotoxic agents have limited efficacy, which necessitates the need for innovative therapeutic approaches. Heat shock protein 90 (HSP90) is overexpressed in a wide range of tumor types including human pancreatic neuroendocrine tumors (PanNETs). Ganetespib is a second-generation HSP90 inhibitor that is well tolerated in cancer patients (dosed into &amp;gt;1500 patients) and is currently being evaluated in several investigator sponsored clinical trials including acute myeloid leukemia (AML), ovarian cancer, breast cancer, and other tumor types. Here, we show that ganetespib inhibits the proliferation of NET cells and induces apoptosis in vitro with potency comparable to another second-generation HSP90 inhibitor (NVP-AUY922), but with potency two- to seven-fold more than first generation inhibitors (17-AAG, IPI-504) in BON-1, CM and H727 cell lines, and thirty-fold more in QGP-1 cell line. In mice bearing PanNET tumor xenografts, single agent ganetespib reduced the growth of tumors without signs of toxicity. Tumors from ganetespib treated animals demonstrated reduced phospho-AKT and phospho-ERK expression, and elevated HSP70 expression, supportive of exposures necessary for functional activity. In an effort to identify clinically meaningful agents that could further potentiate the antitumor activity of ganetespib, we performed in vitro combination screens evaluating proliferation in four NET cell lines with ganetespib and forty FDA approved anticancer agents. Ganetespib showed synergistic effects when combined with inhibitors of mTOR, topoisomerase I or II, or DNA synthesis. Results from our ongoing in vivo combination studies with ganetespib and these three classes of anticancer agents will be presented. Citation Format: Chung Wong, Evan Vosburgh, Arnold Levine, David Proia, Eugenia Xu. Preclinical investigation of the HSP90 inhibitor, ganetespib, in combination with FDA-approved cytotoxic agents for their potential anti-tumor effects on human neuroendocrine tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 267.
Branched chain RNA in situ hybridization for androgen receptor splice variant AR-V7 as a prognostic biomarker for metastatic castration-sensitive prostate cancer.
Authors: Richard J. Lee, Philip James Saylor, Kshitij S. Arora, Vikram Deshpande, Rong Hu, Kara M. Olivier, Erika D. Barrett, Miguel N. Rivera, David Tsai Ting, Chin-Lee Wu, David Tomoaki Miyamoto
Journal: Journal of Clinical Oncology (2016)

e16571 Background: The androgen receptor (AR) mRNA splice variant AR-V7 has emerged as a predictive biomarker for response to AR targeted therapies. There are currently no commercially available assays to detect AR splice variants. The branched chain RNA in situhybridization (ISH) platform enables the highly sensitive detection of RNA transcripts in formalin-fixed, paraffin-embedded (FFPE) tissues. Methods: We designed a branched chain RNA ISH probe to target the unique cryptic exon CE3 of AR-V7 using multiple tiling probes. This automated ISH assay was applied to tumor tissue from two distinct clinical cohorts that we hypothesized to differ in AR-V7 status. A semiquantitative scoring method was used to score the RNA ISH signal in FFPE tissue. We then assessed pre-treatment AR-V7 status as a biomarker in a pilot evaluation of men with treatment-naive metastatic prostate cancer. All evaluations were retrospective. Results: We detected AR-V7 in all tumor samples from men who had metastatic castration-resistant prostate cancer with tissue obtained after disease progression despite at least one subsequent line of hormonal therapy (abiraterone, enzalutamide, or bicalutamide; n = 12). We did not detect AR-V7 in any tumors from men who had undergone prostatectomy for Gleason 6 adenocarcinoma (n = 10). Given the apparent binary distinction of AR-V7 signal among the above groups, we analyzed pre-treatment AR-V7 status as a predictive and prognostic biomarker in men with treatment-naive metastatic disease with long-term follow-up at our institution (n = 22). Patients with metastases but without detectable AR-V7 RNA at baseline had significantly longer overall survival (logrank P = 0.044) and a trend toward superior progression-free survival (logrank P = 0.055). Conclusions: Within an institutional cohort, the RNA ISH assay identified AR-V7 from conventionally prepared FFPE tissue and may have prognostic value in metastatic castration-sensitive prostate cancer. These preliminary findings warrant further study in larger cohorts.
Abstract 4731: Targeted therapies for prostate cancer: Strategies for efficient combinatorial approaches
Authors: Nasir A. Butt, Swati Dhar, Avinash Kumar, Agnes M. Rimando, Xu Zhang, Anait S. Levenson
Journal: Cancer Research (2016)

Abstract Metastasis-associated protein 1(MTA1) is a cancer progression- related epigenetic regulator, which is overexpressed in hormone-refractory and metastatic prostate cancer (PCa). MTA1/HDAC unit is a part of the multi-protein nucleosome remodeling and deacetylation (NuRD) complex. In our previous studies we found that MTA1 expression is significantly increased in prostate-specific Pten-null model, and that potent natural analog of resveratrol, pterostilbene (PTER), exerts its anti-tumorigenic effects by blocking MTA1-associated inactivation (deacetylation) of tumor suppressors. SAHA (suberoylanilide hydroxamine, vorinostat) is a histone deacetylase (HDAC) inhibitor that has been shown to be an effective inhibitor of tumor cell growth. We hypothesize that targeting MTA1/HDAC unit of NuRD complex using PTER in combination with SAHA could act additively or synergistically to block prostate tumor progression in vivo with higher efficacy and lower toxicity. In the current study, we utilized the prostate-specific Pten-null mouse model to evaluate the MTA1/HDAC mediated anti-cancer efficacy of combinatorial approach for dietary PTER and clinically approved HDAC inhibitor, SAHA. After a series of carefully designed breeding strategies and genotyping, we collected 30 prostate-specific luciferase expressing Pten knockout (Pten f/f; Rosa26Luc/+; Pb-Cre4) male mice for our experiments. Prostate-specific luciferase expression allowed non-invasive monitoring of prostate tumor growth in these animals. Mice were randomized into four groups: Vehicle control (10% DMSO); PTER (10 mg/kg bw) alone, SAHA (50 mg/kg bw) alone, and PTER + SAHA. Compounds were injected daily, i.p., starting at 8 weeks of age. Mice were sacrificed at week 18. Histopathological (H&amp;E, SMA, CK-8), immunohistochemical (Ki-67, cleaved caspase-3, CD31) and molecular evaluation (MTA1, pAkt, AR) of prostate tissues showed beneficial effects of treatments alone and more so in combination compared to the control group. Citation Format: Nasir A. Butt, Swati Dhar, Avinash Kumar, Agnes M. Rimando, Xu Zhang, Anait S. Levenson. Targeted therapies for prostate cancer: Strategies for efficient combinatorial approaches. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4731.
Abstract 363: Establishment of multicellular tumor spheroids-based assay for screening of novel therapeutics
Authors: Yeonhwa Song, Haengran Seo
Journal: Cancer Research (2016)

Abstract 3D cell culture system is highlighted as new method to screen for new cancer therapies. The multicellular tumor spheroid cultures are closely similar to pathophysiological gradients of in vivo tumors and subsequently an ideal screening model for new drugs. Hepatocellular carcinomas (HCC) is resistant to conventional chemotherapeutic agents and remains an unmet medical need. Hence, we focused in developing tumor spheroids-based screening assay to identify new drugs to treat HCC. Tumor spheroid cultures were formed in hydrogel coated multi-well plates within 3 days followed by 3 days treatment with reference compounds (Doxorubicin, Etoposide, Methotrexate, Taxol, etc.). Bright images of tumor spheroids were visualized by Operetta imaging system in the presence and absence of reference compounds. Cell viability of spheroids were measured by resazurin assay. In the results, assay was developed and validated using multicellular tumor spheroids (MCTS) cultures composed of Huh7 (HCC cells), WI38 (fibroblasts), LX2 (hepatic stellate cells) and HUVEC (endothelial cells) to recapitulate HCC tumor microenvironments. We also addressed the effect of sorafenib on the growth of spheroids composed of Huh7 alone or MCTS. Results from this study indicate that sorafenib was less efficacious (IC50 = 8.0μM) in the MCTS compared to its effect on Huh7 spheroid (IC50 = 3.8 μM). In summary, we have established and validated a highly reproducible MCTS-based assay. Based on this results, MCTS based-HTS system can offer a new model for drug screening and significantly improve the efficiency of identifying new drugs for liver cancer therapy. Citation Format: Yeonhwa Song, Haengran Seo. Establishment of multicellular tumor spheroids-based assay for screening of novel therapeutics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 363.
Abstract 5106: Unexpected roles for stromal MMP3 during breast cancer
Authors: Emilia Hartland, Charley Jang, Ricardo Romero Moreno, Megan McGarel, Sunil Badve, Laurie Littlepage
Journal: Cancer Research (2016)

Abstract Matrix metalloproteinases (MMPs) are a family of proteases that have been shown to contribute to the degradation of components of the extracellular matrix and other substrates to promote cancer progression and metastasis. Stromelysin / matrix metalloproteinase-3 (MMP3) is one member of the matrix metalloproteinase family that is overexpressed in human breast cancer. During breast cancer, MMP3 is expressed primarily by stromal cells but also by cancer cells. Overexpression of MMP3 induces an epithelial-to-mesenchymal transition (EMT), promotes hyperplastic growth, and expands a mammary gland stem cell population. In addition, MMP3 is required for the mammary gland stem cell population. In this study, we determined if stromal MMP-3 is required for breast cancer progression for primary and metastatic lung tumor growth. To study this, we transplanted mammary epithelial cancer cells (V0PyMT) into the mammary glands of MMP3 knockout and heterozygous syngeneic mice. We quantified the tumor burden of both primary and metastastic tumors over time and discovered that elimination of stromal MMP3 increased the tumor burden. The tumor pathologies, proliferation rate, and apoptosis were similar between cancer and not cancer tissue. In contrast, the vasculature density decreased. These data suggest that stromal MMP3 inhibits, but is not required for, the development of the primary breast tumor. However, in contrast to our primary tumor data, we interestingly discovered that stromal MMP3 was required for visible lung metastases. These experiments begin to distinguish between the contrasting roles of stromal and epithelial MMP3 during breast cancer. Our data reveal that MMP3 contributes to the metastatic tumor formation within the lungs. This study will help to elucidate new mechanisms through which MMP3 functions within particular microenvironmental contexts during breast cancer progression. Citation Format: Emilia Hartland, Charley Jang, Ricardo Romero Moreno, Megan McGarel, Sunil Badve, Laurie Littlepage. Unexpected roles for stromal MMP3 during breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5106.
NCCN's Commitment to Medication Safety: The Vincristine Initiative
Authors: Jessica Sugalski, F Marc Stewart, Robert W Carlson
Journal: Journal of the National Comprehensive Cancer Network (2016)

The mission of NCCN is to improve the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Improving medication safety is an important aspect of fulfilling this mission. In September 2014, the NCCN Best Practices Committee began a medication safety initiative to improve the safe use of vincristine. This article describes and discusses this initiative.