tbuckley/cabot-search huggingface dataset:
Overlapping phenotypes with AFAP and FAP in patients with Lynch syndrome gene mutations.
Authors: Erin Heckaman, Kelsey Moyes, Christopher Arnell, Michelle Landon, Richard J. Wenstrup
Journal: Journal of Clinical Oncology (2014)

402 Background: Lynch syndrome is a well-described cause of hereditary colon cancer. A point of the Amsterdam II criteria, which defines Lynch syndrome, is to exclude familial adenomatous polyposis (FAP). FAP is caused by mutations in the APC gene and is defined as the presence of 100+ adenomas. The attenuated form of familial adenomatous polyposis (AFAP) can be considered when an individual has 10-99 adenomas. While adenomatous polyps may be a part of the Lynch syndrome phenotype (as a precursor to carcinoma), the assumption is that Lynch syndrome and APC-associated polyposis do not have overlapping phenotypes. Methods: A retrospective analysis was performed on 8,202 individuals with a personal history of adenomatous polyps that had clinical genetic testing for Lynch syndrome (including genes MLH1, MSH2, MSH6, PMS2, and EPCAM) between January 2006 and July 2013. Patient adenoma history was collected on the test request form. The inclusion criterion was limited to personal history of adenomatous polyps and did not depend on personal or family history of cancer. Patients were excluded if the test performed was either targeted mutation testing or single gene testing, presumably based on prior immunohistochemistry tumor testing. Results: Of 8,202 patients with a personal history of adenomatous polyps that underwent Lynch syndrome testing, 610 (7.4%) were positive for a mutation. Mutations were detected in patients with a wide distribution of cumulative adenomas (Table). Seventy-five of the patients with a Lynch syndrome mutation had an adenomatous polyp phenotype suggestive of either FAP (100+ adenomas) or AFAP (10-99 adenomas). Of these 75 patients, 19 underwent APCtesting, all of whom were negative for a mutation. Conclusions: Individuals with an adenoma history, who were tested for Lynch syndrome, had an overall 7.4% mutation positive rate, indicating an overlapping phenotype between Lynch syndrome and FAP/AFAP. This overlap supports consideration of a gene panel test approach. [Table: see text]
Cannabidiol: State of the art and new challenges for therapeutic applications
Authors: Simona Pisanti, Anna Maria Malfitano, Elena Ciaglia, Anna Lamberti, Roberta Ranieri, Gaia Cuomo, Mario Abate, Giorgio Faggiana, Maria Chiara Proto, Donatella Fiore, Chiara Laezza, Maurizio Bifulco
Journal: Pharmacology & Therapeutics (2017)
Community health attitude transformation through colon cancer prevention awareness campaign, Lubbock Colorectal Cancer Demonstration Project (LCCDP)
Authors: D. Vugrin
Journal: Journal of Clinical Oncology (2008)

15066 Background: Over 80% of colorectal cancer (CRC) can be prevented from occurring and most deaths could be avoided if the best currently available screening and treatment technology is applied to the entire population at risk according to the American Cancer Society (ACS). Barriers to achieving this are community attitudes and lack of organizational, financial and societal commitment. In 2003, LCCDP was initiated with the objective to transform community health attitudes through a colon cancer prevention awareness campaign, with the goal that 70% of 50-year and older living in Lubbock County receive CRC screening according to ACS guidelines by 2008 and 90% by 2011. This should reduce CRC incidence and decrease age-adjusted CRC mortality in the County by at least 50%. Method: LCCDP Task Force partnered with city, county and state governments, media, academic and health institutions, businesses, work-sites, voluntary organizations, private and state institutions and CRC survivors. The community coalition has conducted CRC prevention awareness campaigns at multiple venues throughout the four years. Results: Analysis of the Behavioral Risk Factors Surveillance System (BRFSS) data showed that the number of 50 year-olds or older screened by colonoscopy/sigmoidoscopy in Lubbock County in pooled 2000–2004 data changed from 48% (sample size 86) to 66% (cl 59.5 - 72.0; sample size 284) in 2006. Colonoscopy/sigmoidoscopy rates were 56.3% in Texas and 57.1 in the USA in 2006. Conclusion: The community-wide CRC prevention awareness campaign has had a positive impact on screening attitudes. Survivors gave a human face to this cancer and tore down the wall of silence around this cancer. The project continues. Supported in part by TCC grants 06–60 and 07–60 No significant financial relationships to disclose.
Patients with melanoma want to know their prognosis and value the use of investigative procedures
Authors: A. Constantinidou, S. Afuwape, T. Hung, K. Acland, C. Healy, A. Ramirez, M. Harries
Journal: Journal of Clinical Oncology (2008)

20751 Background: Users’ views are vital for planning effective cancer services. Little is known of the requirements of patients with melanoma for information on disease status and likely outcomes. Methods: The primary aim of this study was to identify the information that melanoma patients want to have about their disease and prognosis. The secondary aim was to ascertain their views on the utility of Positron Emission Tomography (PET) scans and sentinel node biopsy (SNB). One hundred patients attending the outpatient clinic participated. English speaking patients with a diagnosis of melanoma of greater than 4 months duration were included. Informational needs and views were elicited using a face-to face semi-structured questionnaire. Patients’ responses were analysed using descriptive statistical methods. Results: The vast majority of participants wanted to know everything about their disease upon diagnosis (88%). They also wanted to know their chances of cure (90%) and expressed their wish to be informed as soon as their disease became metastatic (93%). The need for prognostic information (>85%) and information on palliative care input if necessary (98%) were also highly valued. More than 70% of the trial subjects expected this information to be given as soon as the cancer had spread and more than 50% expected the doctor to impart this information without negotiation. Only 33% of responders felt the doctor alone should decide if they should have a regular PET scan whereas 50% felt it should be their decision. These patients emphasised their need for awareness and reassurance. Thirty-eight percent of those who had a SNB had wanted to get as much information about their disease as possible whereas 48% had undergone the procedure because the doctor had suggested it. Patients over 60 were significantly more likely to be doctor led compared to younger patients (p=0.017). Conclusions: Patents with melanoma want detailed and prompt information about their disease including prognosis. Regular PET scans are valued by many patients. The role of SNB is not clear to all patients and older patients need more support to make their own decisions. No significant financial relationships to disclose.
Design of an open-label randomized phase II trial examining the effect of sequencing of sipuleucel-T and androgen deprivation therapy (ADT) on immune markers in prostate cancer patients with a rising prostate specific antigen (PSA) after primary therapy.
Authors: E. S. Antonarakis, A. S. Kibel, D. W. Lin, R. C. Tyler, M. Tabesh, C. G. Drake
Journal: Journal of Clinical Oncology (2011)

TPS189 Background: In the US, 20-40% of men with localized prostate cancer fail primary therapy (surgery or radiation), as indicated by a subsequent rise in PSA. These patients are often treated with ADT to lower their PSA and delay the onset of metastatic disease. In addition, ADT has been shown to enhance anti-tumor immune responses and to augment various cancer immunotherapies. Sipuleucel-T is an FDA-approved autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Sipuleucel-T is given as a series of 3 infusions and designed to induce an antigen-specific immune response against prostate cancer. Here, we propose a clinical trial combining ADT with sipuleucel-T that investigates the influence of treatment sequence on markers of immune response in non-metastatic prostate cancer patients with a rising PSA after primary therapy. The primary study objective is to determine which treatment sequence leads to a superior augmentation of immune markers: ADT started before or after sipuleucel-T. Secondary objectives include: the safety profile of sipuleucel-T in this patient population and the maintenance of immune markers over time. Methods: 60 subjects will be randomized (1:1) to receive sipuleucel‐T followed by ADT (given 2 wks after the 3rd immunotherapy infusion), or ADT followed by sipuleucel-T (given 3 mo after ADT initiation). In both arms, ADT treatment will continue through Month 18. Patients will be stratified by 1) PSA doubling time (≤3 mo, >3 to ≤12 mo), and 2) radical prostatectomy (RP) or radiation therapy (XRT) or RP plus salvage XRT. Cellular and serological immune responses will be assessed before and after sipuleucel-T infusions 1, 2, and 3 and at the following time points after the 3rd infusion: weeks 2, 6, 12 and months 6, 9, 12, 15, and 18. PSA and testosterone will be monitored every 3 months through Month 18. Immune marker responses will be compared between groups to determine the importance of ADT and sipuleucel-T sequencing.
Neoadjuvant chemotherapy and prognostic subgroups defined by survival benefit in patients with locoregionally advanced nasopharyngeal carcinoma.
Authors: X. Ji, Y. Zhong, Y. Zhou, F. Zhou, G. Zhang, G. Chen, D. Deng, H. Liu, J. Zhang, C. Xie
Journal: Journal of Clinical Oncology (2011)

5536 Background: To evaluate the contribution of neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to identify the prognostic subgroups that could benefit the most from neoadjuvant chemotherapy. Methods: From 2004 through 2009, 164 patients with stage II to IVb NPC were treated by radiotherapy alone (RT; n = 74) or chemoradiotherapy (RT/CT; n = 90). All patients received 68-70 Gy to the nasopharynx. Neoadjuvant chemotherapy consisted of 2-4 cycles of cisplatin and 5-fluorouracil, or cisplatin and docetaxel every 3 weeks. Both groups were well-matched for prognostic factors except cancer stage, with more advanced NPC in RT/CT. Results: With a mean follow-up of 34.5 months, the 3-year actuarial rates of overall survival (OS), disease-free survival (DFS), metastasis-free survival and relapse-free survival for RT/CT and RT alone groups were 84.3% v 78.2% (Log-rank P = 0.132), 81.2% v 58.3% (Log-rank P = 0.024), 86.4% v 71.4% (Log-rank P = 0.029) and 94.8% v 79.8% (Log-rank P = 0.114), respectively. Using the Cox model adjusted for prognostic factors, improvement in OS on RT/CT was significant (P = 0.049). Stratification analysis showed that DFS improvement was pronounced in the following prognostic subgroups: stage IV, T3/T4 stage, N2/N3 stage, non-keratinizing carcinoma, youngers, males, smokers, drinkers and patients without family history of cancer. Conclusions: Neoadjuvant chemotherapy improves OS, DFS and MFS for locoregionally advanced NPC, and DFS improvement was pronounced in some prognostic subgroups. Such work could be helpful to guide effective therapy of individuation.
Randomized, controlled trial comparing S-1 with UFT/LV as adjuvant therapy for curatively resected stage III colorectal cancer (BCOG-CC02 study).
Authors: Keiji Koda, Hideaki Miyauchi, Kimiyoshi Yokoi, Chihiro Kosugi, Takashi Kaiho, Susumu Kobayashi, Takenori Ochiai, Hisahiro Matsubara
Journal: Journal of Clinical Oncology (2013)

520 Background: Oral anticancer drug, UFT/LV, has recently been reported to improve both overall survival (OS) and relapse free survival (RFS) for patients with Stage III colorectal cancer in Japan. We conducted a randomized clinical trial to compare S-1 with UFT/LV for adjuvant therapy in patients with Stage III colorectal cancer. Methods: Patients with Stage III colorectal cancer (PS, 0 to 1; age, 20 to 80 years) were randomized to take either UFT / LV (28 days per 5 weeks) for 6 months. or S-1 (28 days per 6 weeks) for 12 months started within 6 weeks following curative resection. We investigated the correlations between disease- free survival (DFS) and tissue mRNA levels of 5-FU and folate metabolism-related enzymes. In addition, we investigated overall survival (OS) and safety. Results: Between April 2008 and August 2010, a total of 145 patients were registered from 22 centers. There were no clear intergroup differences in background factors. The patients who relapsed during protocol duration of treatment were excluded, the percentages of patients who took expected dosage of medicine were 67.1% (47/70) and 87.3% (62/71) in S-1 and UFT/LV groups, respectively. Grade3 to 4 myelosuppression(4%), bilirubin(3%) and diarrhea(8%) were occurred in S-1 group whereas, grade 3 liver dysfunction (5%) and diarrhea (5%) occurred in UFT/LV group, but all of them were reversible. The median follow-up period was 934 days, 3-years’ DFS in patients of S-1 and UFT/LV groups were 65.9% and 72.7%, respectively (p=0.88). In a univariate analysis, topoisomerase-1 (TOPO-1) mRNA level was shown as a factor of the recurrences. A poor-prognosis patient population was observed in the S-1 group such as with low gamma-glutamyl hydrolase (GGH) mRNA level. Conclusions: Oral anticancer drug, S-1 showed an equivalent effect for UFT/LV in Stage III colorectal cancer as adjuvant therapy. Tissue levels of mRNA of 5-FU/ folate metabolism-related enzymes were important parameters for postoperative prognosis in patients with stage III colorectal cancer who take oral 5-FU derivatives for adjuvant therapy. Clinical trial information: UMIN000001560.
Interventional pain management in cancer patients: Experience from tertiary care center of India
Authors: S. Bhatnagar, S. Mishra
Journal: Journal of Clinical Oncology (2008)

20739 Background: Oral medication of WHO ladder is a gold standard and the mainstay of cancer pain management. It gives pain relief in 85–90% cases. In remaining 10–15% patients, physicians keep on fighting to give adequate pain relief.Interventional pain management techniques could be a very good alternative option for such patients. The key requirement for successful nerve block is to ensure optimal distribution of local anesthetic around nerve and plexus structures. The recent use of ultrasound imaging for nerve localization is an innovative application of an old technology, which addresses many of the shortcomings of current techniques. Methods: This article describes five years of experience of using diferent interventional pain management technique used on patients not relieved by oral medication at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi. Results: Total number of patients that received interventional block (=215). Mandibular nerve block (=100), Coeliac plexus block (=26), Hypogastric plexus block (=22), Stellate ganglion block (=20), Occipital nerve block (=12), Gloosopharyngeal nerve block (=12), Supraorbital nerve block (=10), Sciatic nerve block (=12), Lumber chemical sympathectomy (=1). Out of the total 215 patients, 184 patients received block either under nerve stimulator guidance, CT guidance or under C- arm guidance. The failure rate ranged from 5–20% with inadequate level of nerve block. Ultrasound guided nerve block has improved quality of nerve block with success rate varying from 95–100%. Complications such as damage to neural structure and intravascular injections are nil. Conclusions: Although in near future routine use of this ultrasound technology for nerve blocks is not possible in most of the centers in India as this technique is quite nascent, require costly equipment and needs advance training, however, authors believe that any technology that can make the procedure better, safer and faster for both the patients and doctors then it must be adopted. No significant financial relationships to disclose.
The Canadian True NTH Initiative: A multisite intervention to improve the lives of men with prostate cancer.
Authors: Julie Gilbert, Matthew M. George, Elilzabeth D. Huggins, Maureen E. Rowlands
Journal: Journal of Clinical Oncology (2016)

118 Background: The True NTH Initiative aims to improve the lives and experiences of men with prostate cancer, as well as those of their partners, family and caregivers. In Canada, Prostate Cancer Canada selected ten teams to develop, implement and evaluate evidence-informed programs focusing on decision support, clinical support, lifestyle management, education, social support, navigation and treatment follow-up. Project teams were encouraged to align their local evaluations with a common evaluation framework and a national evaluation plan was developed. The aim of this abstract is to share methodology and early results of a multi-level evaluation that will address a range of programs designed to improve the lives of men with prostate cancer. True NTH is funded globally by the Movember Foundation, and operates in Canada, USA, UK, Australia, New Zealand, Ireland and Singapore. Methods: Projects (Solutions) selected for the initiative had existing evidence for their efficacy. Project teams were responsible for designing the implementation of their Solution and an appropriate evaluation. Local and national evaluations used a recognized framework (RE-AIM) to systematically study the real world uptake of these interventions, focusing on questions of Reach, Effectiveness, Adoption, Implementation, and Maintenance. Project teams provide quarterly narrative updates and annual written reports with quantitative measures and narrative components. Key informant interviews with project leads will complete the final national evaluation. Results: To date, projects have generated learning across different provincial health systems, academic institutions and community settings. Teams have learned to address challenges of participant recruitment and project endorsement, and have begun to appreciate the benefits of collaboration. Teams have also reflected on the importance of engaging clinicians in the implementation of their Solutions for effective uptake and sustainability. Conclusions: The results of the ongoing multi-level evaluation continue to provide insight into real world implementation of evidence-informed programs and the critical factors that enable their effectiveness.
Effect of catumaxomab on EpCAM+ tumor cells in vitro in the presence of immune effector cells from ovarian cancer patients treated with chemotherapy.
Authors: K. Pietzner, J. Sehouli, J. Atz, K. Dettmar, H. Martinius, R. Spannagl, D. Seimetz, P. Schroeder, H. Lindhofer, G. Oskay-Özcelik, R. Chekerov, E. I. Braicu
Journal: Journal of Clinical Oncology (2011)

e13043 Background: The trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the intraperitoneal treatment of malignant ascites. Since chemotherapy may impair the functionality of immune cells required for catumaxomab’s mode of action, this study investigated the potential influence of chemotherapy treatment of patients with ovarian cancer on the anti-tumor activity of catumaxomab. Methods: Immune cells of patients taken at different time points before/after chemotherapy treatment were used to assess catumaxomab-mediated cytotoxicity in vitro. A total of 22 ovarian cancer patients were selected for the analysis. Patients had received carboplatin/paclitaxel (1st-line treatment) or topotecan or doxorubicin monotherapy as 2nd–x-line treatment, respectively. Peripheral blood was collected and purified patient PBMCs were used as effector cells to determine catumaxomab-mediated cytotoxicity in a co-culture test system with SK-OV-3 ovarian tumor cells as EpCAM+ target cells. Results: No significant interference of chemotherapeutic treatment on catumaxomab-mediated tumor cell killing was observed. Activity in vitro varied when comparing patient’s immune cells to healthy control PBMCs. However, for all patient samples efficient elimination of tumor cells was demonstrated at catumaxomab concentrations that correspond to the therapeutic dose range. Conclusions: Catumaxomab induces a potent destruction of EpCAM+ tumor cells with immune effector cells from ovarian cancer patients treated with chemotherapy. Thus, these nonclinical data provide a pharmacological basis for the integration of catumaxomab therapy into chemotherapeutic regimens.
Identification of diagnostic and prognostic miRNAs in human bladder cancer by microarray expression profiling
Authors: Lars Dyrskjot, Helle Erbs Toldbod, Anne Birgitte Als, Claus Andersen, Klaus Jensen, Torben Orntoft
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

1777 

Bladder cancer is the fourth most common malignancy in males in the western countries. The disease presents in two different forms: superficial tumors (stage Ta and T1), and muscle invasive cancers (stage T2-4). Superficial tumors form a heterogeneous group, spanning from completely benign, non-invasive papillary tumors, which rarely progress, to papillary lamina propria invasive high grade tumors, which progress to muscle invasive cancer in of up to 60% at long term follow-up. Prognostic markers for prediction of disease progression of superficial tumors are highly needed. Furthermore, markers for response to chemotherapy and survival are needed for advanced muscle invasive cancers. Small non-coding microRNAs (miRNA) were identified recently as regulators of gene expression. miRNAs are involved in cancer development and progression acting as tumor suppressors and oncogenes and several miRNAs have been reported to have diagnostic and prognostic value.

Here we profiled the expression of miRNAs in bladder cancer using spotted LNA based oligonucleotide microarrays (miRCURY™ LNA Array Probeset V7.1). Probes were spotted in duplicate on CodeLink slides. A miRNA pool from all samples was generated and used as common reference sample. Two μg of each sample and 2 μg reference sample were labelled for each microarray expiriment using Hy3 and Hy5 respectively. Following hybridisation and scanning raw expression data was Lowess normalized using TIGR MIDAS 2.19 software and TIGR MeV 3.1 was used for subsequent data analysis. Results were validated by QPCR.

By comparing the miRNA expression between 11 normal bladder biopsies, 13 Ta tumors (5 progressing to T2-4), 26 T1 tumors (11 progressing to T2-4) and 26 T2-4 tumors we identified several miRNAs with significant differential expression. We identified 17 miRNAs significantly regulated between normal and cancer; amongst others miR-126, miR-145, miR-143 and miR-21 previously found to be regulated in cancer. We identified 29 miRNAs differentially expressed between superficial and muscle invasive tumors. We found no difference between Ta and T1 tumors. When comparing non-progressing to progressing tumors, as well as when comparing patients that survived chemotherapy to those that succumb, sets of miRNAs were detected that differed between the patent groups. However, independent validation in larger tumor materials is required and will be presented at the meeting. These findings indicate that miRNA markers may, in combination with e.g. gene expression markers, help guide patient treatment in the future.