tbuckley/cabot-search huggingface dataset:
Characterization of serum proteome in patients with metastatic colorectal cancer responsive and nonresponsive to bevacizumab using 2 d-DIGE.
Authors: Petra Martin, Sinead Noonan, Blathnaid Nolan, Caitriona Scaife, Giuliano Elia, Diarmuid O'Donoghue, David William Fennelly, Jacintha O'Sullivan
Journal: Journal of Clinical Oncology (2012)

484 Background: Treatment of patients with metastatic colorectal cancer includes chemotherapy and a monoclonal antibody (cetuximab or bevacizumab). Patients who have k-ras mutated tumors are given bevacizumab. However, no biomarker exists to determine those patients who will respond to this targeted treatment. The objective of this study was to investigate the differential protein expression between patients who do and do not respond to bevacizumab and also compare this with normal controls. Methods: Serum from 24 patients diagnosed with metastatic colorectal cancer and 11 normal controls were collected pre-treatment. All patients received bevacizumab along with chemotherapy. Progression free and overall survival data was collected on all patients. Serum was depleted of high abundant proteins and protein expression analysed using fluorescence two-dimensional differential in-gel electrophoresis (2 D-DIGE). Gels were scanned using a Typhoon 9410 Variable Mode Imager (GE Healthcare) and exported into Progenesis SameSpots v3.3 (Nonlinear Dynamics, UK) for quantitative analysis. Selected differentially expressed were excised, digested with trypsin and analysed using the LTQ-Orbitrap XL mass spectrometer. Results: 66 proteins were identified to be statistically expressed between the responders and non-responding group (p&lt;0.05). 30 proteins were differentially expressed between the cancer and normal group (p&lt;0.05). Conclusions: There is a significant difference in protein expression patterns between responders and non responders to bevacizumab. Further screening required to assess for instability proteins that may have functional importance in governing treatment resistance.
Interim analysis of CALGB 150607: A pilot project to study the expression of MET and P53 in resected lung adenocarcinoma specimens.
Authors: A. K. Salama, H. Pang, R. A. Kratzke, W. G. Richards, E. E. Vokes, R. Salgia
Journal: Journal of Clinical Oncology (2010)

10633 Background: MET is a receptor tyrosine kinase that has been shown to be dysregulated in a number of malignancies, including non-small cell lung cancer (NSCLC). In patients with NSCLC, alterations in MET, and its ligand, HGF, have been associated with higher pathological stage and worse outcome in a number of smaller studies. The primary objective of this study is to determine the correlation between MET expression with stage and overall survival in adenocarcinoma (AC) patients in a large series of patients. The secondary objectives are 1) to determine the correlation with MET mutations, epithelial mesenchymal transition (EMT), EGFR mutations and expression, KRAS mutations, and P53 mutations and expression with respect to survival; and 2) to determine the impact of MET amplification on prognosis. Methods: MET, EGFR exons 18-21, P53 exons 4-10, and KRAS exon 2 were sequenced using standard PCR and sequencing techniques. Standard immunohistochemistry (IHC) techniques were used to evaluate total MET, phosphorhylated (p)MET (Y1003 and Y1230/34/35), P53, HGF, EGFR and E-cadherin expression. Quantitative PCR was used to determine MET gene copy number. A total of 280 patients will be included in this study, and an interim analysis will be presented here. Results: Immunohistochemical data is available for 20 patients. High expression of total MET was seen in 95% of patients, high Y1003 MET expression was seen in 80% of patients, high Y1230/34/35 MET expression was seen in 55% of patients. Six out of 40 patients have been found to carry a mutation in the MET gene; three of these represent novel mutations in the semaphorin and juxtamembrane domains that have not been previously reported in the literature. MET amplification data will be forthcoming. Conclusions: Both MET and pMET are highly expressed in resected lung adenocarcinoma specimens. Novel MET mutations have been identified in key domains. Updated results and correlation with overall survival will be presented. No significant financial relationships to disclose.
<i>NTRK3</i> as a novel tumor suppressor gene in colorectal cancer.
Authors: Yanxin Luo, Andrew Kaz, Samornmas Kanngurn, William M. Grady
Journal: Journal of Clinical Oncology (2012)

469 Background: Neurotrophin tyrosine kinase receptor 3 (NTRK3) is a receptor tyrosine kinase that has been shown to be an oncogene in breast cancer and possibly in hepatocellular carcinoma. NTRK3 is a trophic dependence receptor, which is a recently described class of receptors that initiate signaling in both the ligand bound and unbound states. Through a genome-wide screen for aberrantly methylated genes, we identified aberrantly methylated NTRK3 as a frequently methylated gene in colon cancer. The aim for the present study is to determine if NTRK3 is an epigenetically silenced tumor suppressor gene in colorectal cancer. Methods: NTRK3 promoter methylation was analyzed in human colon cancer cell lines, normal colon epithelium tissue, colorectal adenomas and colorectal cancers using quantitative methylation-specific PCR and bisulfite sequencing. NTRK3 mRNA and protein expression were studied using quantitative real-time PCR, immunohistochemistry and western blotting respectively. The tumor suppressor function of NTRK3 was examined by assessing the effect of NTRK3 on cell apoptosis, cell migration and in vitro colony formation assays in colon cancer cell lines stably transfected with an NTRK3 expression construct in the presence or absence of NT-3. Results: NTRK3 is methylated in 60% of colon adenomas and in 57% of colorectal cancers. The aberrant methylation of NTRK3 suppresses NTRK3 expression and releases colon cancer cells from NTRK3 mediated apoptosis induced by the expression of NTRK3 in the absence of the ligand NT-3 via the activation of MAPK/ERK pathway. Methylation of NTRK3 also releases colon cancer cells from NTRK3 mediated suppression of motility and anchorage independent growth. The addition of NT3 to colon cancer cells transfected with NTRK3 inhibits the tumor suppressor effects of NTRK3. Conclusions: The aberrant methylation of NTRK3 is likely functionally relevant for colorectal cancer formation as NTRK3 appears to be a conditional tumor suppressor gene in the colon depending on the expression status of its ligand NT-3. NTRK3 is a novel aberrantly methylated conditional tumor suppressor gene that is frequently methylated in colon adenomas and cancers and whose discovery reveals possible novel treatment approaches to colon cancer.
Oral sex may transmit HIV.
Authors: Scott Gottlieb
Journal: BMJ (2003)

Laboratory studies of mouth tissue suggest that unprotected oral sex does have the potential to transmit HIV.

A US research team examined the possibility that normal human oral keratinocytes might be directly infected by HIV or might convey infectious HIV virions to adjacent leucocytes.

Dr Xuan Liu of Charles R Drew University of Medicine and Science in Los Angeles and colleagues at the University of California in Los Angeles obtained oral tissue samples from over 50 healthy, HIV negative patients and exposed the tissue to three different types of HIV. They found that two of the types could infect and reproduce within keratinocytes lining the surface of the mouth and that these cells can then transfer the infection to adjacent white blood cells (Journal of Virology 2003;77:3470-6) . 

“HIV is able to get into [keratinocytes], but it reproduces less than it would in blood cells… because saliva contains an HIV inhibitor,” Dr Liu said. Under certain circumstances, he said, keratinocytes can release the virus to blood cells, which proliferate much faster than keratinocytes.
Final analysis of dose density with zoledronic acid treatment in metastatic breast cancer patients: ZARAS study.
Authors: J. De la Haba, A. Rodriguez-Lescure, J. M. Baena, J. Martin Liberal, S. Morales, J. I. Chacon, J. M. Lopez-Vega, I. Fernandez, D. Aguiar, A. Garcia-Palomo, R. M. Llorente, J. L. Barea, E. Alvarez, I. Blancas, Y. Fernandez, P. Sanchez Rovira, G. Vinyes
Journal: Journal of Clinical Oncology (2011)

630 Background: Zoledronic acid (ZA), a highly potent bisphosphonate, has been shown to reduce/delay skeletal-related events (SREs) in patients (pts) with bone metastatic disease, and extending time to first skeletal complication, which can have a positive impact on the quality of life of pts with bone metastasis. Our aims were to determine treatment adherence, patterns of use (regular administration q 3-4 weeks) and maintenance doses of ZA in breast cancer pts with bone metastasis (mBC) in Spain. Methods: Retrospective observational, multicentric study. Data from 421 mBC pts died (before 31st of March 2009), were collected. 366 pts, with at least 3 consecutive doses of ZA treatment for their metastatic disease, were included in this final analysis report. Results: n= 366 pts. Median age was 57 years (28-86). Postmenopausal status 69.4%, ER+ 77%, HER2/neu+ 25,7%, PR+ 52,2%. 51,6% of pts had previous SREs. 50% pts received > 12 dose of ZA during the first year of treatment (optimal treatment); 32.5% during the second year. There was a significant difference in median time to disease progression between patients with a regular administration (> 12 doses yearly during 2 years) vs patients treated with irregular patterns (17,3 months - 10,1 months) (P= .001). Median time of overall survival (OS) after first dose of ZA was 32.7 months in pts who received an optimal/regular treatment (OT) during the first 12 months and 50,7 months in pts with OT during 24 months vs. 26.1 months in pts. with a sub-optimal dose during entire treatment persiod (P= .001). Conclusions: In Spain, adherence to the recommended dose of ZA was suboptimal. Most patients were not treated with optimum doses. Regular dosing with ZA resulted in a significant improvement in patient outcomes (time to disease progression and OS).
Time from nephrectomy (Nx) as an independent prognostic factor in metastatic renal cell carcinoma (mRCC) patients treated with targeted therapies (TTs).
Authors: Giuseppe Procopio, Roberto Iacovelli, Elena Verzoni, Paolo Grassi, Isabella Testa, Enrico Garanzini, Nicola Nicolai, Filippo G. De Braud
Journal: Journal of Clinical Oncology (2014)

517 Background: Nx has been established as a prognostic factor in mRCC and included in current prognostic classifications. Despite this, the prognostic value of time from Nx has not well established in patients (pts) treated with TTs. We aim to investigate if the time from Nx to diagnosis of metastatic disease is a prognostic factor in mRCC pts treated with TTs. Methods: Database of pts treated at Istituto Nazionale Tumori of Milan, was reviewed. Only pts who received an Nx were included in the final analysis. For each pt time from Nx to diagnosis of metastatic disease was collected and pts were divided in three groups based on time ≥ 1 year (A), &lt; 1 year (B) or Nx performed at diagnosis of metastatic disease (C, cytoreductive). Age, sex, ECOG performance status and MSKCC prognostic group were also collected. Overall survival was calculated from the start of therapy to death or last follow-up. Median OSs were estimated with Kaplan-Meier method and compared with log-rank test; association of factors with survival was evaluated with Cox-analysis. Results: A total of 285 pts meet the inclusion criteria: median age was 60.8 y (IQR: 52.5 – 68), 73% were males; ECOG-PS was 0 in 61%, 1 in 34% and 2 in 5%. Prognosis based on MSKCC classification was good in 36%, intermediate in 49% and poor in 15%, and its prognostic value was confirmed (HR: 2.7; 95%CI, 2.1 – 3.4, p&lt;0.001). Time from Nx was ≥ 1 year in 25%, &lt; 1 year in 26% and concomitant to diagnosis of metastatic disease in 49% of cases. The median survival was 44.5 (95%CI, 35.6 – 53.5), 22.3 (95%CI, 16.1 – 28.5), 18.1 months (95%CI, 11.5 – 24.6) for the group A, B and C, respectively with a significant differenced for every comparison (A vs. B: p=0.041; A vs. C p&lt;0.001 and B vs. C p=0.016). When time from Nx was compared to MSKCC in the multivariable analysis, this remain an independent prognostic factor (HR: 0.7; 95%CI, 0.6 – 0.9, p&lt;0.001). Conclusions: In mRCC pts treated with Nx and targeted therapy, time from Nx is an independent prognostic factor. Pts with good prognosis based on MSKCC criteria who had Nx more than 1 year before the diagnosis of metastatic disease have better prognosis compared to a pts with the same MSKCC risk that receive Nx with cytoreductive intent.
The association of long pentraxin 3 on prognosis in pancreatic carcinoma patients on gemcitabine-based chemotherapy.
Authors: S. Kondo, H. Ueno, C. Morizane, F. Koizumi, K. Tamura, T. Okusaka
Journal: Journal of Clinical Oncology (2011)

10536 Background: Advanced pancreatic carcinoma (PC) has a poor prognosis, nevertheless, gemcitabine and FOLFILINOX have been established as the standard chemotherapy. We previously reported that C-reactive protein (CRP) is one of the prognostic markers in advanced PC. CRP, serum amyloid P component and long pentraxin 3 (PTX3) belong to the pentraxin family of pattern recognition molecules involved in acute-phase response and innate immunity. Inflammatory mediators present in the tumor milieu may promote cancer progression and are considered promising targets for novel biological therapeutic approaches. Methods: We used PC cell lines (MIA Paca-2, AsPC-1, BxPC-3 and PANC-1) to validate the expression of PTX3 levels (Perseus Proteomics Inc.) using an enzyme-linked immunosorbent assay (ELISA) and examined cell biology with a migration and invasion assay. Moreover, we have prospectively assigned chemotherapy naïve advanced PC patients to estimate the relation between the clinical manifestation and the plasma PTX3 levels. Survival analysis and statistical testing for independent prognostic factors were performed using log-rank tests and Cox regression. Results: In vitro, we could show that MIA Paca-2 and PANC-1 highly express PTX3. High levels of expression of PTX3 in PC cells are associated with promoting paracrine PTX3 from the monocyte cell line (THP-1). Moreover, PC cells overexpressing PTX3 promote migration and invasion. In advanced PC patients (n = 70), and the mean PTX3 level at baseline was 5.23 ± 3.84 ng/mL (range: 0.9-17.7 ng/mL). In this population, 17 out of 70 patients were defined as having high PTX3 expression (cut off, 5.2 ng/mL). The median overall survival times were 265 days in PTX3low and 112 days in PTX3high (Log-rank: p = 0.001). The median progression free survival times were 109 days in PTX3low and 80 days in PTX3high (Log-rank: p = 0.27). A Cox multivariate analysis showed that high PTX3 levels were associated with the mortality risk. Conclusions: PTX3 as a clinical biomarker is one of the prognostic factors for advanced PC and can be considered as a promising target of novel biological therapy for PC.
Implementing a comprehensive physician-communication-skills improvement initiative: The Cleveland Clinic experience.
Authors: Timothy D. Gilligan, Adrienne Boissy, Amy Windover, Jessica Crow
Journal: Journal of Clinical Oncology (2013)

186 Background: Physician communication skills are associated with important outcomes, including medical results, treatment adherence, malpractice claims, patient safety, and physician satisfaction. Recently, patient satisfaction with physicain communication became a factor influencing Medicare reimbursement. In 2010, the Cleveland Clinic began building a physician communication training program to improve doctor communication skills. Methods: Following a literature review and a survey of communication skills programs at a variety of U.S. hospitals, we collaborated with the American Academy of Communication in Healthcare (AACH) to develop a full-day course based on Frankel and Stein’s Four Habits model. The model emphasizes skills related to initiating the encounter, eliciting the patient’s story, expressing empathy, educating the patient and collaboratively developing a plan. The course was designed to be taught by physicians and was highly experiential and skills based, making extensive use of role-play exercises. An AACH consultant trained 15 physicians to teach the course during several 7-day train-the-trainer courses. Results: Between September 2011 and May 2013, over 800 physicians took the course. It became very popular and has been consistently oversubscribed. For the first 450 physicians trained, we reviewed patient satisfaction survey scores for the 6 months before and after they took the course. For all 13 items on the Press Ganey ambulatory patient survey used, scores were higher after taking the course. For 7 of the 13, the difference was statistically significant (p values ranging from .003 to .044). Conclusions: Our experience with communication skills training indicates that such training can be well received by physicians if it is high quality. Key elements of our program that we believe contributed to its success are the following: it was developed by physicians for physicians; it is taught by physicians with substantial clinical practices so that the atmosphere is colleagues teaching colleagues; and it is skills based rather than cognitive in focus so that participants have tangible tools that they can use in their practice.
A comparative study of a monoclonal antibody against EGFR (nimotuzumab) used in combination with chemoradiation versus chemoradiation alone in the treatment of locally advanced inoperable squamous cell carcinoma of the head and neck.
Authors: Aseem Rai Bhatnagar, Dharam Pal Singh
Journal: Journal of Clinical Oncology (2012)

51 Background: To determine the efficacy, safety and tolerability of concurrent nimotuzumab (monoclonal antibody against epidermal growth factor receptor) used in combination with chemoradiation versus chemoradiation (CRT) alone in advanced inoperable squamous cell carcinoma of the head and neck (SCCHN). Methods: 56 patients were randomly assigned to either of the two treatment arms, nimotuzumab + CRT arm and CRT alone arm. Both arms received concurrent Cisplatin 30 mg/m 2 repeated weekly for 6-7 cycles along with external beam radiotherapy 64-70 Gy (200cGy/day for 5 days a week for 6-7 weeks). Nimotuzumab arm additionally received nimotuzumab 200 mg weekly for 6-7 cycles. The patients were followed for 6 months after completion of CRT. The study end points were tumor response evaluation according to the RECIST Criteria version 1.1 and safety analysis using RTOG Acute Radiation Morbidity Scoring Criteria. Patients were evaluated weekly with hematologic tests and for adverse events like mucositis and dermatitis during the CRT. Tumor assessment was performed with clinical and endoscopic methods regularly during the CRT and then at 1 month, 3 months, and 6 months intervals after CRT. One MR imaging was done before starting the CRT to evaluate the baseline tumor characteristics, and another was done after the completion of CRT either at 3 months or 6 months or at both the intervals. Results: 25 patients each were evaluable in both the arms who completed the 6-month study. The overall response rate (complete response + partial response) was 96% in nimotuzumab + CRT arm, whereas it was only 72% in CRT alone arm after 6 months of completion of CRT, which is statistically significant (p value = 0.0206 by Chi Square test). Additionally, nimotuzumab did not potentiate toxicities of CRT, and there was no significant difference in the acute radiation mucositis, dermatitis, or hematological toxicities in both the groups (p value&gt;&gt;0.05). Conclusions: Nimotuzumab can be safely added to the standard CRT treatment for advanced inoperable SCCHN, to achieve better tumor response without potentiating toxicity.
An automated system for insuring monitoring of myelosuppression in patients receiving self-administered oral chemotherapy.
Authors: Robert Morrell, Janet Tooze, Michele Harmon, Annette Carter, Alisha Detroye, Glenn Jay Lesser
Journal: Journal of Clinical Oncology (2012)

296 Background: Protracted outpatient oral chemotherapy regimens have created new challenges for monitoring patients for toxicity. Unlike IV chemotherapy which guarantees clinician access to the patient before proceeding with therapy, oral agents can continue to be taken despite missed follow-up visits and lab draws. After observing patients return from unrecognized lapses in monitoring with severe myelosuppression, we sought to retrospectively measure risks and to prospectively test a software-based monitoring system designed to flag and notify team members of missed lab monitoring. Methods: We evaluated 117 patients who had received a standard 42-day continuous course of oral temozolomide as therapy for newly diagnosed primary malignant brain tumors to assess monitoring compliance, as well as adverse events. Standard practice is to obtain a weekly CBC with differential and platelets during the 6 weeks of concurrent chemoradiation. Grade 3 or higher hematologic events were observed in 9 (7.7%) patients. Gaps in monitoring were defined as no testing for 10 days or more, and were classified as minor (10-12 days) and major (13-27 days). Results: 34 (29.1%) patients had one or more gaps during treatment; 19 (16.2%) had majors and 18 (15.4%) had minors. 2 of the patients with gaps in coverage exhibited grade 3 or 4 myelosuppression upon their return to monitoring. We have currently monitored 36 patients prospectively with prototype software designed to email staff whenever a patient was not monitored for 7 days or had scheduled visits too far in the future. The software uses data downloaded from the electronic medical record (12,889 labs, [908 pertinent], 441 visits) and was effective in finding patients that missed labs or did not get properly scheduled visits. Five such mistakes were detected and 4 were corrected based on the system flag. Problems encountered were mainly false positives associated with entry of chemotherapy stop dates. Conclusions: Monitoring failures pose risks to patients receiving oral chemotherapy and traditional medical information systems make detection of missing data difficult. Systems such as ours are simple to build and could be integrated with most EMR systems.