tbuckley/cabot-search huggingface dataset:
2-MPPA, a selective inhibitor of PSMA, delays prostate cancer growth and attenuates taxol-induced neuropathy in mice
Authors: Y. She, Z. Tang, R. G. Lapidus, K. M. Wozniak, H. I. Scher, B. S. Slusher
Journal: Journal of Clinical Oncology (2005)

8054 Background: Docetaxel is a standard of care treatment for patients with progression castration resistant prostate cancer, from which peripheral neuropathy may be dose limiting. A selective inhibitor of PSMA, termed 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA), both prevents and reverses taxol-induced neuropathy in murine models, as indicated by deficits in sensory nerve conduction velocity (SNCV). 2-MPPA, a potent (IC50 of 90 nM) and selective inhibitor of glutamate carboxypeptidase (GCPII), also known as PSMA or NAALADase was also able to delay tumor growth in a prostate cancer model expressing high levels of PSMA. Of importance, there was no change in efficacy when taxol was administered with 2-MPPA in this model. Methods: Neuropathy: Female DBA2 mice received 5 mg/kg taxol (5 i.p. doses in two weeks) or 25 mg/kg taxol (4 i.p. doses in two weeks) with daily 30 mg/kg 2-MPPA or vehicle. Neuropathy was indicated by a SNCV deficit compared to baseline (pre-chemotherapy) values. Cancer: nu/nu mice with or with out testosterone supplements were inoculated with CWR22 or CWR22RS tumor. When tumors reached 50mm3, mice were dosed with 2-MPPA (10 to 750 mg/kg) bid PO for two weeks and tumor volume was monitored. Results: 2-MPPA significantly prevented the deficit in SNCV induced by both 5 and 25 mg/kg taxol by 96.3 ± 4.4% and 98.3± 11.6% respectively (p<0.001). Moreover, 7-day p.o. treatment with 30 mg/kg 2-MPPA given after a persistent SNCV deficit was established reversed the decline in SNCV by 98.3±8.0% (p<0.05). Peripheral nerve histopathology evaluations are ongoing. In a separate study, 10 mg/kg 2-MPPA inhibited tumor growth in the high expressor PSMA model CWR22RS by 70% (p<0.03). Lastly, 2-MPPA was dosed concomitantly with a therapeutic dose of taxol in the hormone-dependent model of prostate cancer, CWR22, and no effect on taxol efficacy was observed. Conclusions: Inhibition of GCPII/PSMA may have a therapeutic potential both as an anti-cancer agent, as well as to reduce chemotherapy-induced neuropathy No significant financial relationships to disclose.
Long-Term Persistence of Monoclonal B Cells After Cure of Helicobacter pylori Infection and Complete Histologic Remission in Gastric Mucosa–Associated Lymphoid Tissue B-Cell Lymphoma
Authors: Christian Thiede, Thomas Wündisch, Birgit Alpen, Beatrix Neubauer, Andrea Morgner, Marc Schmitz, Gerhard Ehninger, Manfred Stolte, Ekkehard Bayerdörffer, Andreas Neubauer
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Cure of Helicobacter pylori infection is associated with remission induction in the majority of patients with low-grade gastric mucosa associated lymphoid tissue (MALT) lymphoma in localized stages; however, limited data exist as to whether these patients may be cured of their lymphoma. The present study was performed to investigate whether the polymerase chain reaction (PCR) for the rearranged immunoglobulin heavy chain region may be used to define “molecular” remission. PATIENTS AND METHODS: Ninety-seven patients who suffered from low-grade gastric MALT lymphoma stage I E were observed with central pathology and molecular biology after cure of H pylori infection. PCR was performed with the use of consensus primers for the framework regions 1, 2, and 3 and monoclonality was corroborated by sequence analysis. In selected cases, microdissection was performed to study the origin of the monoclonal B cells. RESULTS: Of the 97 patients, 77 obtained complete endoscopic and histologic remission (CR). Twenty of 44 patients with PCR monoclonality at diagnosis and with sufficient molecular follow-up displayed monoclonal bands for a median time of 20.5 months after CR (range, 0 to 50.4 months). These B cells were related to the original lymphoma clone by sequence analysis. Microdissection analysis identified basal lymphoid aggregates as the source of these monoclonal B cells. Local relapse occurred in and was observed by PCR in four patients. All four patients displayed monoclonal PCR before relapse, and three of these four showed ongoing PCR monoclonality throughout their course, indicating the persistence of malignant cells. CONCLUSION: Half of all patients with gastric MALT lymphoma show long-term PCR monoclonality up to several years after cure of H pylori infection and CR. Patients with monoclonal PCR should be observed closely, whereas long-term PCR negativity may indicate cure of the disease.
Hemorrhagic Lesions Produced by Claude's Chicken Tumor-10 Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Pearson, John W., Groupé, Vincent
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article Hemorrhagic Lesions Produced by Claude's Chicken Tumor-10 Virus Get access John W. Pearson, John W. Pearson Institute of Microbiology, Rutgers University, New Brunswick, New Jersey 08903 Search for other works by this author on: Oxford Academic PubMed Google Scholar Vincent Groupé Vincent Groupé Institute of Microbiology, Rutgers University, New Brunswick, New Jersey 08903 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 42, Issue 5, May 1969, Pages 723–732, https://doi.org/10.1093/jnci/42.5.723 Published: 01 May 1969 Article history Received: 04 September 1968 Accepted: 31 January 1969 Published: 01 May 1969
Prescriptions for hydrocodone plummet after US tightens prescribing rules
Authors: Michael McCarthy
Journal: BMJ (2016)

Prescriptions for combination analgesics containing the opiate hydrocodone have fallen by 22% since the US government imposed tougher prescribing rules in 2014, a study has found.1 Hydrocodone bitartrate, which is often formulated with a non-opioid analgesic such as paracetamol, is one of the most commonly misused prescription opioids in the United States.

In October 2014, in response to a growing opioid use epidemic, the US Drug Enforcement Administration tightened prescribing requirements for hydrocodone combination products by moving them from schedule III of the Controlled Substances Act to the more restrictive designation of schedule II.

Under schedule …
A phase Ib dose-escalation study of binimetinib (MEK162) in combination with weekly paclitaxel in patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.
Authors: Rachel N. Grisham, Michael S. Gordon, Wael A. Harb, Carol Aghajanian, D. Scott McMeekin, Kristin McKinley, Lisa Renee Anderson, Renae Chavira, Janna Christy-Bittel, Emma Barrett, Kathleen N. Moore
Journal: Journal of Clinical Oncology (2015)

5516 Background: Ovarian cancer is associated with key genetic alterations, including those that lead to activation of the RAS/RAF/MEK/ERK pathway. Binimetinib (BINI) is a potent, selective, allosteric inhibitor of MEK1/2. This study determined the recommended phase II dose (RP2D) of BINI administered on 2 dosing schedules in combination with weekly paclitaxel (PAC) and assessed the safety, pharmacokinetics (PK) and preliminary antitumor activity in female patients (pts) with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer. Methods: BINI was administered orally either on a continuous (CONT) schedule at 30 mg twice daily (BID; dose level 1 [DL1]) or 45 mg BID (DL2), or on an intermittent (INTERM) schedule on Days (D) 1-5 weekly for 3 of every 4 weeks (q3/4w) at 45 mg BID, in combination with PAC 80 mg/m2 IV on D1 weekly q3/4w. Results: Thirty-four pts were enrolled and treated, with 22 pts on the CONT schedule (14 at DL1; 8 at DL2) and 12 pts on the INTERM schedule. The median age was 63 years (range 42-77), baseline ECOG PS was 0 or 1 (97%), median number of prior systemic therapies was 4 (range 1-14) and the majority of tumors were high-grade serous (HGS; 74%) or low-grade serous (LGS; 18%). On the CONT schedule, dose-limiting toxicities (DLTs) of fatigue, nausea, neutropenia, rash and stomatitis were observed; the RP2D was declared as BINI 30 mg BID CONT with weekly PAC. On the INTERM schedule, a DLT of asthenia was observed; the RP2D was confirmed as BINI 45 mg BID INTERM with weekly PAC. The most common Grade 3/4 AEs included anemia (18%), vomiting (12%), and fatigue, nausea, neutropenia, pulmonary embolism, small intestinal obstruction and stomatitis (9% each). When administered in combination, no clinically relevant differences in BINI or PAC exposures were observed. Of the 29 pts with measurable disease, the response rate was 17% with 1 complete response (LGS) and 4 partial responses (1 LGS, 3 HGS). Conclusions: In this pt population, the combination of BINI on both the CONT and INTERM schedules with weekly PAC had an acceptable safety and PK profile at the RP2Ds. Responses were observed in HGS and LGS pts. Clinical trial information: NCT01649336.
Survival rates in HLA-A2 positive patients, with stage III-IV serous adenocarcinomas of the ovary, correlates with increased expression of COX-2 and iNOS, loss of MHC Class I and II and defects of the antigen processing mechanisms at the tumour level
Authors: E. Andersson, C. C. Johansson, L. Villabona, L. Kanter, H. Helgadottir, T. Dalianis, K. Bergfeldt, B. Seliger, S. Ferrone, R. Kiessling, G. V. Masucci
Journal: Journal of Clinical Oncology (2008)

16544 Background: We have shown that the high prevalence of HLA-A2 in Scandinavia is associated to poor prognosis in advanced (stage III-IV) serous adenocarcinoma of the ovary. Our objective was to analyse whether there exists a relationship between the expression of HLA molecules and components of the antigen processing pathway as well as the presence of high COX-2 activity and the patients´ survival. Methods: To test our hypothesis, 40 Swedish women with epithelial ovarian cancer were selected from an unbiased database of ovarian cancer patients at our department. Their HLA haplotypes were defined by the PCR/sequence-specific oligonucleotide hybridization method (PCR/SSOP) Tissue slides from paraffin embedded tumour material were stained with antibodies recognising COX-2, iNOS, MHC-class I/II heavy chain (HC) and molecules of the antigen processing machinery (APM). The probability of survival was defined by Kaplan-Meier analysis. Results: HLA-A2 positive patients, in stage III-IV were distinguished with high production of COX-2 and iNOS, lack of heavy chain (HC) MHC-class I/ II and defects in APM components. They were found to have the poorest survival rates when compared to the rest of the patients in the group (p< 0.01) Conclusions: Our results indicates a possibility to identify a high risk group of ovarian cancer patients by linking together antigen presenting capacity, histological type and clinical stage to a series of negative prognostic factors at the tumour level. Our finding might have a relevant impact on future management of these patients. Further analyses will be extended to an entire database of 300 patients. No significant financial relationships to disclose.
제10차 춘계 학술대회 초록집 : 구연 6 ; 만성 C형 간염환자의 배우자에서 C형 간염 특이 T 세포의 반응
Authors: 김창욱, 윤승규, 왕진상, 장우임, 남순우, 최종영, 한준열, 한남익, 이창돈, 정규원, 서희식
Journal: Clinical and Molecular Hepatology (2004)
Hypoxia-Induced Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma Induces an Immunosuppressive Tumor Microenvironment to Promote Metastasis
Authors: Long-Yun Ye, Wei Chen, Xue-Li Bai, Xing-Yuan Xu, Qi Zhang, Xue-Feng Xia, Xu Sun, Guo-Gang Li, Qi-Da Hu, Qi-Han Fu, Ting-Bo Liang
Journal: Cancer Research (2016)

Abstract Portal vein tumor thrombosis (PVTT) is a significant risk factor for metastasis in hepatocellular carcinoma (HCC) patients and is therefore associated with poor prognosis. The presence of PVTT frequently accompanies substantial hypoxia within the tumor microenvironment, which is suggested to accelerate tumor metastasis, but it is unclear how this occurs. Recent evidence has shown that the hypoxia-inducible factor HIF-1α induces epithelial-to-mesenchymal transition (EMT) in tumor cells to facilitate metastasis. In this study, we investigated whether hypoxia-induced EMT in cancer cells also affects immune cells in the tumor microenvironment to promote immunosuppression. We found that hypoxia-induced EMT increased the expression of the CCL20 cytokine in hepatoma cells. Furthermore, coculture of monocyte-derived macrophages with hypoxic hepatoma cells revealed that the expression of indoleamine 2, 3-dioxygenase (IDO) was induced in monocyte-derived macrophages in a CCL20-dependent manner. In turn, these IDO-expressing monocyte-derived macrophages suppressed T-cell proliferation and promoted the expansion of immunosuppressive regulatory T cells. Moreover, high CCL20 expression in HCC specimens was associated with PVTT and poor patient survival. Collectively, our findings suggest that the HIF-1α/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network. Cancer Res; 76(4); 818–30. ©2016 AACR.
Prediction of Response to Adrenalectomy in the Treatment of Advanced Breast Cancer
Authors: Ihor J. Masnyk, Debra T. Silverman, Benjamin F. Hankey
Journal: JNCI Journal of the National Cancer Institute (1978)

A collaborative study was done that was aimed at the development of a prognostic index for the assignment of patients with metastatic breast carcinoma to bilateral adrenalectomy for palliation. A total of 121 patients treated by adrenalectomy was analyzed; 28 remissions occurred for an overall remission rate of 23%. When used in its original form, Bulbrook's discriminant was not useful as a predictive index for the patients. Only 21 of 88 patients (24%) with positive discriminants had a remission, whereas 7 of 33 patients (21%) with negative discriminants had a remission. Replacing etiocholanolone with androsterone improved the performance of the discriminant, inasmuch as 21 of 73 patients (29%) with positive discriminants had a remission and 7 of 48 patients (15%) with negative discriminants had a remission; however, the association of the discriminant with remission was not statistically significant. Our approach to the development of a new predictive index was based on the logistic regression model as representing the relationship between concomitant information and the probability of remission. Three steroid quantities were found to have an apparent relationship with remission: androsterone plus etlocholanolone, total 17-ketogenic steroids, and 3α, 17α, 21-trihydroxy-5 β-pregnane-11, 20-dione/3 α, 17 α, 21-trihydroxy-5 α-pregnane-11,20-dione. However, the relationships of the three steroid quantities to remission were not highly statistically significant, which raised-doubts as to whether the results obtained here would be replicated with another set of data. The comparison of our findings with those of a recent study on the use of estrogen receptor determinations in predicting response to endocrine therapy suggested that, for this purpose, such determinations were superior to the measurement of urinary steroid metabolites. However, because of the selection that occurs in the identification of patients for adrenalectomy and the variation in the history of previous treatments, results of the study of response to endocrine therapy and the development of predictors may have little general application because the assumption that a study group of patients is a sample from a definable population may have little validity.
Bioactivity of C3H and RIII Mammary Tumor Viruses in Virgin Female BALB/c Mice: Brief Communication 2
Authors: Francesco Squartini, Maria Bistocchi
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Bioactivity of C3H and RIII Mammary Tumor Viruses in Virgin Female BALB/c Mice: Brief Communication Get access Francesco Squartini, M.D., Francesco Squartini, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria Bistocchi, M.D. Maria Bistocchi, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 6, June 1977, Pages 1845–1847, https://doi.org/10.1093/jnci/58.6.1845 Published: 01 June 1977 Article history Received: 09 August 1976 Accepted: 08 December 1976 Published: 01 June 1977
HLA Antigen in Chinese Patients With Hepatocellular Carcinonas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S H Chan, M J Simons, C J Oon
Journal: JNCI Journal of the National Cancer Institute (1980)

One hundred and fourteen Chinese patients with hepatocellular carcinomas (HCC) were studied for alpha-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), anti-HBsAg, and HLA markers. Younger patients with HCC (less than 60 yr old) were more significantly associated with elevated serum AFP (P less than 0.0001) and serum HBsAg (P less than 0.0001) than were older (greater than or equal to 60 yr old) patients. A strong correlation existed between serum AFP and HBsAg among the patients (P less than 0.0001). Of 27 AFP-negative patients, 15 (55.6%) had HLA-B15 compared to 53 of 238 (22.3%) healthy controls (corrected P less than 0.003, relative risk = 4.4). The frequency of HLA-B15 was even higher in the AFP-negative plus HBsAg-negative subgroup (61%). AFP-negative patients also had a significant lack of blood group A.
Late intensive combined modality therapy followed by autologous bone marrow infusion in extensive-stage small-cell lung cancer.
Authors: D C Ihde, A B Deisseroth, A S Lichter, P A Bunn, D N Carney, M H Cohen, S R Veach, R W Makuch, A Johnston-Early, R A Abrams
Journal: Journal of Clinical Oncology (1986)

To attempt to improve the poor prognosis of extensive-stage small-cell lung cancer (SCLC) patients, we tried to administer late intensive combined modality therapy (LICMRX) to patients with good tumor regression after 12 weeks of conventional chemotherapy. Twenty-nine consecutive extensive-stage SCLC patients received 6 weeks of cyclophosphamide, methotrexate, and lomustine (CMC) induction therapy, followed by 6 weeks of vincristine, doxorubicin, and procarbazine (VAP). After restaging for assessment of tumor response, autologous bone marrow (ABM) was collected in patients in good medical condition with complete response (CR) or partial response (PR) and no tumor on marrow examination. LICMRX consisted of irradiation with 2,000 rad in five fractions for five days to sites of initial tumor involvement, followed by cyclophosphamide, 60 mg/kg for 2 days, and etoposide, 200 mg/m2 for 3 days and then by ABM infusion. Prophylactic cranial irradiation (PCI) was administered thereafter, but no further chemotherapy was used. Due to lack of tumor regression or poor medical condition, only ten of the original 29 patients were eligible for LICMRX; two refused, so only eight (28%) received therapy. Three patients who began LICMRX in CR developed recurrence of SCLC after an additional 4, 8, and 15 months. Of five patients with PR, one attained CR but relapsed at 3 months, two remained in PR and progressed at 2 and 4 months, and two died of infection without recovery from LICMRX. Mean time from ABM infusion to recovery of granulocyte count to 500/microL was 15.8 days in the six surviving patients (range, 12-22). The major non-hematologic toxicity of LICMRX was severe esophagitis. Among all 29 patients, there were six CRs (21%) and no 2-year survivors, compared with a CR rate of 36% and 10% 2-year survivors in 78 extensive-stage patients previously treated with CMC plus VAP without LICMRX. We conclude that the LICMRX given in this study can be administered to only a minority of extensive-stage SCLC patients and is very unlikely to yield substantial improvement in the fraction of 2-year survivors (95% confidence limits for 2-year survival 0% to 10%).
Identification of the causes that influence recruitment in oncology clinical trials (OCT)
Authors: L. E. Fein, A. Romera, C. M. Micheri, M. I. Diaz, R. A. Sala
Journal: Journal of Clinical Oncology (2009)

e17562 Background: Prediction of patient recruitment in OCT is one of the most important variables to guarantee timely closure of the trial. Earlier data analysis and conclusions define further research or discontinuation of the development of a given drug. Methods: Retrospective analysis of the recruitment and clinical records of all the patients of the COR that were contacted to participate in an OCT from 2006 to 2008 to identify the causes according to which patients did not participate. Results: Total of candidates 346, 175 women (50.6%). Average age 60 years (range 36 to 89). 42 patients (12%) rejected to participate in an OCT. 80 patients (23%) were screening failures (SF). 59 patients (17%) for not fulfilling an inclusion criteria (IC). Non appropriate stage or absence of measurable disease at screening (35%), abnormal labs (14%) and state of receptors or biomarkers (9%). Total of clinically unpredictable IC SF was 57.5%. 21 patients (6%) were SF due to an exclusion criteria (EC). Presence of distant metastases (12,5%), abnormal labs (2.5%) and abnormal EKG (2.5%). Total of clinically unpredictable EC SF was 19%. Conclusions: 35% of candidate patients did not participate. The most frequent cause was SF (23%). 76.5% of these SF were impossible to determine when informed consent was signed. 12% of patients rejected to participate for different reasons. Our results did not identify a predominant modifiable reason to improve recruitment. For future feasibility analyses our estimation of 35% dropout will be considered standard. [Table: see text] No significant financial relationships to disclose.
Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial
Authors: Mieke L G ten Eikelder, Katrien Oude Rengerink, Marta Jozwiak, Jan W de Leeuw, Irene M de Graaf, Mariëlle G van Pampus, Marloes Holswilder, Martijn A Oudijk, Gert-Jan van Baaren, Paula J M Pernet, Caroline Bax, Gijs A van Unnik, Gratia Martens, Martina Porath, Huib van Vliet, Robbert J P Rijnders, A Hanneke Feitsma, Frans J M E Roumen, Aren J van Loon, Hans Versendaal, Martin J N Weinans, Mallory Woiski, Erik van Beek, Brenda Hermsen, Ben Willem Mol, Kitty W M Bloemenkamp
Journal: The Lancet (2016)
Internet surveillance systems for early alerting of health threats
Authors: J P Linge, R Steinberger, T P Weber, R Yangarber, E van der Goot, D H Al Khudhairy, N I Stilianakis
Journal: Eurosurveillance (2009)

In order to gather a comprehensive picture of potential epidemic threats, public health authorities increasingly rely on systems that perform epidemic intelligence (EI). EI makes use of information that originates from official sources such as national public health surveillance systems as well as from informal sources such as electronic media and web-based information tools.