tbuckley/cabot-search huggingface dataset:
Colorectal cancer and DNA mismatch repair proteins in young patients: Study in a Mexican population.
Authors: Angel Admin Lara Carbarin, Oralia Barboza Quintana, Raquel Garza Guajardo, Natalia Vilches Cisneros, Juan Francisco Gonzalez Guerrero, Juan Pablo Flores Gutierrez
Journal: Journal of Clinical Oncology (2015)

e14522 Background: Colorectal cancer (CRC) is the fourth most common neoplasm worldwide and the incidence in young patients is reported to be increasing. In Mexico there are few studies that examine CRC in this population. Objective: To determine the clinicopathological and molecular characteristics of CRC tumors in a group of young patients from a large hospital in northeastern Mexico. Methods: Data was collected from pathology reports and patient files from 1987 to 2014 on cases from partial or total colectomy specimens with an available tissue sample in patients younger than 50 years. Immunohistochemistry for DNA mismatch repair (MMR) proteins MLH1 and MSH2 was realized in all cases and BRAF V600E mutation status was investigated in selected cases. 95% confidence intervals were calculated for the whole population and χ2 test was performed for comparison between groups according to MMR protein status. Results: Data was collected on 91 cases, almost half of them were proximal tumors (48.35%, 95%CI 37.7 to 59.0%) or had a MMR protein expression defect (45%; 95%CI 34.6% to 55.8%). One third had either family history or had developed a second primary neoplasm at diagnosis or in the following years (31.4%, 95%CI 20.8 to 46.3%). When comparing between groups depending on the status of MMR protein expression there was a statistically significant difference for proximal location (p = 0.029) and family history (p = 0.018) in the group with MMR protein deficiency. None of the patients investigated had the BRAF V600E mutation. Conclusions: Previously unreported, MMR-deficient CRC has a high prevalence in a group of young Mexican patients. This finding correlates with the high prevalence of proximal colon tumors identified in the study. One third of patients had either family history of CRC or a second primary neoplasm which could suggest a familial cancer predisposition like Lynch syndrome or some other form of familial cancer. Absence of BRAF V600E mutation increases this probability. Further studies are required to establish the true incidence of these syndromes and to assess the impact of MMR protein deficiency on treatment response and survival in the Mexican population.
Unusual Presentations of Germ Cell Tumors
Authors: Lisa Horvath, Mathew Bayfield, Anthony Clifford, Dorothy Painter, Stephen Clarke
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.3.909 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11157044 Unusual Presentations of Germ Cell Tumors Case 1. Recurrent Laryngeal Nerve Palsyin Mediastinal Seminoma Lisa HorvathxLisa HorvathSearch for articles by this author , Mathew BayfieldxMathew BayfieldSearch for articles by this author , Anthony CliffordxAnthony CliffordSearch for articles by this author , Dorothy PainterxDorothy PainterSearch for articles by this author , Stephen ClarkexStephen ClarkeSearch for articles by this author Show More Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, Australia https://doi.org/10.1200/JCO.2001.19.3.909 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Detection of Occult Invasion in Melanoma in Situ—Reply
Authors: May P. Chan, Douglas R. Fullen, Timothy M. Johnson
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Effect of Melan-Α/Μart-1-peptide vaccination plus IMP321 on antitumor immunity and clinical benefit in patients receiving autologous PBMCs after lymphodepletion.
Authors: Emanuela Romano, Helene Bichat, Athina Stravodimou, Pedro Romero, Speiser E Daniel, Frederic Triebel, Olivier Michielin, Alexander Harari, Serge Leyvraz
Journal: Journal of Clinical Oncology (2013)

e20011 Background: Immunotherapy offers great promise for cancer treatmet. Strong evidence supports adoptive cell transfer (ACT) and immunemodulation for regression of advanced melanoma. Few studies assessed the potential synergy between these two strategies. Methods: Twelve patients with metastatic melanoma received multiple Melan-A/Mart-1-peptide vaccinations with (n=6) or without (n=6) IMP321 (LAG-3Ig fusion protein) as an adjuvant in combination with lymphodepleting chemotherapy and ACT. All patients were selected on the basis of ex vivo detectable Melan-A-specific CD8 T cell responses and were immunized at day (D) 0, 8, 15, 22, 28, 52, and 74 post-reinfusion. Results: One-week after reinfusion of bulk autologous PBMCs, a significant expansion of Melan-A-specific CD8 T cells was measured in &gt;83% (n=5) and &lt;17% (n=1) of patients from the IMP321 and control groups, respectively (p=0.02). Compared to the control group, the mean fold increase of Melan-A-specific CD8 T cells was respectively &gt;2-, &gt;4-, and &gt;6-fold higher in the IMP321 group at D15, D30, and D60 (p=0.02). A long-lasting Melan-A-specific CD8 T-cell response was significantly associated with IMP321 (p&lt;0.001). A higher proportion of Melan-A-specific CD8 T EMRA (i.e., CD45RA+CCR7-CD127-) cells was observed in the IMP321 group at the peak of the response (p &lt;0.002), whereas no significant difference was observed in the expression of co-inhibitory receptors (i.e., PD-1, 2B4, TIM3, CD160). IMP321 was associated with a significantly (p&lt;0.04) reduced expansion of regulatory T cells (T REGS ); we observed a negative correlation between the fold increase of Melan-A-specific CD8 T cells and the relative expansion of T REGS. Clinical benefit (assessed as CR, PR, and SD) was observed in none of the control patients vs 67% (4/6) of patients from the IMP321 group, (p=0.02). Conclusions: Vaccination with IMP321 as an adjuvant in combination with lymphodepleting chemotherapy and ACT provided clinical benefit and this was associated with a more robust and durable cellular antitumor immune response, supporting further development of IMP321 for future immunotherapeutic strategies. Clinical trial information: NCT00324623.
Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression
Authors: Becker M.P. Law, Ray Wilkinson, Xiangju Wang, Katrina Kildey, Mae Lindner, Melissa J. Rist, Kenneth Beagley, Helen Healy, Andrew J. Kassianos
Journal: Kidney International (2017)

Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3-CD56+) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry. At a subset level, both the CD56dim NK cell subset and particularly the CD56bright NK cell subset were elevated in fibrotic kidney tissue. However, only CD56bright NK cells significantly correlated with the loss of kidney function. Expression of the tissue-retention and -activation molecule CD69 on CD56bright NK cells was significantly increased in fibrotic biopsy specimens compared with non-fibrotic kidney tissue, indicative of a pathogenic phenotype. Further flow cytometric phenotyping revealed selective co-expression of activating receptor CD335 (NKp46) and differentiation marker CD117 (c-kit) on CD56bright NK cells. Multi-color immunofluorescent staining of fibrotic kidney tissue localized the accumulation of NK cells within the tubulointerstitium, with CD56bright NK cells (NKp46+ CD117+) identified as the source of pro-inflammatory cytokine interferon-γ within the NK cell compartment. Thus, activated interferon-γ–producing CD56bright NK cells are positioned to play a key role in the fibrotic process and progression to chronic kidney disease.
Phase I-II trial of concomitant pre-operative hyperfractionated radiotherapy and gemcitabine for locally advanced rectal cancers
Authors: A. S. Allal, S. Bieri, P. Gervaz, C. Soravia, P. Gertsch, P. Morel, A. D. Roth
Journal: Journal of Clinical Oncology (2004)

3678 Background: To determine the maximum tolerated dose (MTD) of gemcitabine when administered concomitantly with hyperfractionated radiotherapy (RT) preoperatively in patients with locally advanced rectal cancers and to investigate the mid-term efficacy of such a regimen. Methods: 37 patients with stages II-III tumors were enrolled. RT consisted in 50 Gy given in 2 daily fractions of 1.25 Gy in 4 weeks. The starting dose of Gemcitabine was 10 mg/m2/day (in a 30 min IV perfusion) twice weekly with planned escalation steps of 5 mg/m2/day. Main end-points for of the study were complete pathological tumor response, the rate of clear margin resection as well as actuarial locoregional control and disease-free survival. The median follow-up for all patients was 32 months (range: 10–51 months). Results: 2/4 patients presented with dose-limiting rectal toxicities at the level of 45 mg/m2 (severe acute proctitis requiring hospitalization in the immediate post-RT period). Thus, the gemcitabine biweekly dose of 40 mg/m2 was considered as the MTD. Among the 36 operated patients, 17 (47%) had a marked pathological response, including 6 patients (17%) with a microscopically complete response and 11 (30%) with only microscopically residual carcinoma of less than 1 cm. All of them had a clear surgical margins. At 3 years actuarial overall survival rate was 85% and locoregional control was 94.5%. Conclusions: In pre-operative treatment of locally advanced rectal cancers, the present study determined the recommended dose of gemcitabine to be 40 mg/m2 when administered biweekly concurrently with 50 Gy hyperfractionated RT. The encouraging pathological response rate and the very low locoregional recurrence rate suggest that this innovative approach merit further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Oncology, Switzerland
Is the Berg axillary lymph node categorization useful in the 3D Era
Authors: A. I. Saito, C. Vargas, R. Benda, C. G. Morris, N. P. Mendenhall
Journal: Journal of Clinical Oncology (2006)

10643 Background: The Berg muscle-based categorization of axillary lymph node location has been used extensively by pathologists and surgeons to describe the extent of axillary node dissection in breast cancer patients, but its reproducibility with different arm positions and its utility in 3-D radiation treatment planning have not been tested. Methods: CT scans were obtained in 16 patients in 2 positions: historic position (HP), arms 90 degrees to the body axis; standard position (SP), arms above head. The volume, contents, and location of each Berg lymph node level (LNL) and the location of lymph nodes, surgical clips, pectoral muscles, and vascular structures relative to reference points were compared between the two scans. Results: Relative to T3, the LNL positions in SP were shifted from HP as follows: Level I, 23.1 mm anteriorly, p &lt; 0.01; Level II, 7.5 mm medially, p = 0.04; Level III, 18.8 mm medially, p = 0.05. The pectoralis major and minor muscles were displaced medially (23.9 mm, p &lt; 0.01 and 7.5 mm, p = 0.09) and anteriorly (18.2 mm, p &lt; 0.01 and 11.2 mm, p &lt; 0.01). At Level I, the axillary vessels (18.0 mm, p &lt; 0.01), subscapular artery (25.4mm, p &lt; 0.01) and lateral thoracic artery (8.4 mm, p &lt; 0.01) were displaced anteriorly. With arm position change, lymph node position moved with vessel position rather than muscle position. Discrepancies were also observed in the number and location of lymph nodes (60%) and clips (66%) in given LNL’s between arm positions. Conclusions: Surgeons, radiologists, and radiation oncologists alike should be aware that lymph node position relative to muscle boundaries will vary significantly with arm position changes, making objective comparisons of information collected in different arm positions unreliable. This has significant implications for radiation treatment planning. No significant financial relationships to disclose.
Treatment “mismatch” in early prostate cancer: An empirical measure of patient-physician communication
Authors: R. C. Chen, J. A. Clark, S. P. Mitchell, J. A. Talcott
Journal: Journal of Clinical Oncology (2004)

4566 Background: Because complications vary by treatment, preexisting organ dysfunction may relatively contraindicate specific treatment modalities for early prostate cancer. However, dysfunction may not be fully communicated between patient and doctor. We compared patient-reported pretreatment dysfunction with the treatment modality received to empirically assess this process. Methods: In a prospective, 438-patient cohort study, we determined how often patients with “intermediate” and “poor” urinary, sexual, and bowel function received relatively contraindicated brachytherapy (BT), nerve sparing radical prostatectomy (NSRP), or external beam radiotherapy (EBRT) respectively. Because age affects treatment choice, we assessed receipt of contraindicated (i.e.,“mismatched”) BT in all men, NSRP in men ≤ 65 years, and EBRT in men >65 years. To assess the actual impact of “mismatched” treatments, we analyzed functional outcomes. Results: Overall, 242 patients reported “intermediate” to “poor” baseline urinary, sexual, and/or bowel function; 50 patients (21%) received “mismatched” treatments. Of 196 patients in our cohort with baseline urinary obstructive/irritative symptoms, 28 (14%) received BT (see table). Of 83 patients 65 years old or younger with intermediate or poor baseline sexual function, 17 (20%) received NSRP. Of 213 patients older than age 65, 7 had baseline bowel dysfunction, but 5 (71%) received EBRT. “Mismatched” patients tended to have greater increases in dysfunction, although small sample sizes limited analysis. Conclusions: Patients reporting dysfunction received relatively contraindicated treatment modalities surprisingly often. While multiple factors affect treatment decisions, incomplete patient-physician communication regarding baseline patient dysfunction may compromise the quality of care. No significant financial relationships to disclose.
Lenalidomide added to bendamustine-rituximab for untreated chronic lymphocytic leukemia (CLL): A phase 1 study.
Authors: Jeremy S. Abramson, Matthew Steven Davids, Lillian Werner, David Christopher Fisher, Philippe Armand, Philip C. Amrein, Donna S. Neuberg, Ephraim P. Hochberg, Jennifer R. Brown
Journal: Journal of Clinical Oncology (2015)

7082 Background: Lenalidomide is an immunomodulator with activity in CLL. Bendamustine-rituximab (BR) is a widely used upfront regimen. We conducted a phase I trial combining lenalidomide (len) with BR. Methods: Patients had untreated CLL with an indication for therapy; ANC ≥ 1000, platelets ≥ 50000; and adequate organ function. A 3+3 design was used with 10 additional patients at the MTD. Escalating doses of len were added to standard dose BR, with bendamustine dosed at 90mg/m2. Len was given on d8-22 in c1, and d1-21 in subsequent cycles. The starting dose level for len was 2.5mg. Level 2 was 2.5mg for c1 and escalated to 5mg with c2. Level 3 was 5mg for c1, then 10mg with c2. Patients could receive up to 6 cycles. All patients received allopurinol, aspirin and pegfilgrastim support. DLT was assessed during c1 of dose level 1, and c1-2 of subsequent dose levels. Results: Twenty-three patients were accrued. Median age was 64 (range 43-85). Thirty-five percent of patients had Rai stage 3/4, 52% had unmutated IGHV, and 26% had 11q deletion. Dose level 2 had one DLT of pulmonary embolism (PE). Dose level 3 was declared the MTD. Eleven subjects completed 6 cycles; median number of cycles was 5 ( < 1-6). Reasons for discontinuation were neutropenia (3), PE (2), rash (2), zoster (1), thrombocytopenia (1), Hodgkin lymphoma transformation(1), withdrawal of consent (1), and physician decision (1). Most common toxicities of any grade were rash (n = 14), fatigue (13), nausea (11), fever (10), anemia (9), thrombocytopenia (6), cough (5), and diarrhea (5). Five patients were suspected of tumor flare, 4 of whom were treated with steroids and the other spontaneously remitted. No tumor lysis syndrome was seen. Grade 3-4 toxicities occurring in > 1 patient were rash (6), neutropenia (4), febrile neutropenia (3), anemia (2), and pneumonitis (2). One subject developed CMV reactivation. Dose reductions were required in 9/13 subjects at the MTD due to neutropenia (6), rash (3) and anemia (1). The ORR was 87% and CRR was 39%. Conclusions: Len-BR results in increased toxicity compared to what would be expected from BR alone, though efficacy was high. Given the rate of toxicities after the DLT assessment period, the 10mg len dose may be too high for most patients. Clinical trial information: NCT01400685.
Abstract P252: Duration and Life-stage of Antibiotic Use and Risk of Cardiovascular Disease in Women
Authors: Yoriko Heianza, Yan Zheng, Wenjie Ma, Tiange Wang, Dianjianyi Sun, Eric B Rimm, Christine M Albert, Frank B Hu, Kathryn M Rexrode, JoAnn E Manson, Lu Qi
Journal: Circulation (2017)

Background and Aims: Growing data suggest that antibiotic use, which may alter the gut microbiome, is related to risk of cardiovascular disease (CVD) and mortality. However, evidence from prospective cohort studies is still scarce; and no large prospective study has investigated associations between cumulative antibiotic use during adulthood and risk of CVD. We aimed to examine duration of antibiotic use and risk of CVD among apparently healthy women from the Nurses’ Health Study (NHS). Methods: This study included 36,922 women without history of myocardial infarction (MI), angina pectoris, stroke, or cancer in the NHS and with available data on total days of antibiotics use per year (0 to &lt;15 days, 15 days to &lt;2 months, or 2 months or more) during ages 20-39, 40-59 and after age 60, as reported on the 2004 questionnaire. Incidence of CVD (MI or stroke) over 8 years was assessed. Hazard ratios (HRs) were estimated as categories of duration of use compared with the none to &lt;15 days per year group, using multivariate-adjusted Cox proportional hazards model including traditional risk factors (such as demographic variables, hypertension, diabetes, hypercholesterolemia, smoking, physical activity, Alternative Healthy Eating Index score, body mass index, aspirin, and anti-inflammatory medication), and reasons for antibiotics use (respiratory infection, urinary tract infections, acne or rosacea, chronic bronchitis, or dental), as well as other medications (such as H2 blockers, proton pump inhibitors), and other diseases (such as lung or kidney disease). Results: As compared to women with “none to &lt;15 days per year of use” during age 40-59 y, those with a history of antibiotics use “15 days to &lt; 2 months” or “2 months or more” had a significantly increased risk of CVD with an adjusted hazard ratio (HR [95%CI])_ of 1.19 (1.03, 1.38) and 1.34 (1.08, 1.66), respectively. Reported use of antibiotics for 2 months or more per year after age 60 was also associated with a HR of 1.24 (1.02, 1.51) for CVD. A longer exposure of antibiotics use was more strongly associated with increased risk of stroke than MI Antibiotic use during young adulthood (age 20-39) was not significantly associated with elevated risk of CVD. Conclusions: Our results suggest greater duration of exposure to antibiotics in middle- and older adulthood may be related to an increased risk of future CVD, independent of traditional risk factors.
Association of sociodemographic factors with nonguideline treatment in papillary thyroid carcinoma.
Authors: Paritosh Suman, Tricia Moo-Young, Richard A Prinz, David J. Winchester
Journal: Journal of Clinical Oncology (2015)

e17096 Background: There is wide variability in the management of papillary thyroid carcinoma (PTC). National Comprehensive Cancer Network (NCCN) and 2009 American Thyroid Association guidelines are currently in practice. In this largest national database study on PTC, we investigated the adherence with guideline concordant therapy and factors related to noncompliance. Methods: The National Cancer Data Base (NCDB) was queried from 2009-2011 for patients with PTC. Predictors of guideline concordant surgery and radioactive iodine (RAI) treatment were determined by logistic regression. Results: Overall, 6372 (29.8%) patients received nonguideline treatment. 1088 (7.4% ) patients had nonguideline surgical management. Females (OR 1.31, 95% 1.05-1.65, P 0.019) and medicare insurance (OR 1.34, 95% CI 1.04-1.72, P 0.025) were positively and academic cancer centers (OR 0.65, 95% CI 0.45-0.95, P 0.023) were negatively associated with noncompliant surgical management. 4955 (28.8% ) patients did not receive RAI when indicated. Females (OR 1.14, 95% CI 1.01-1.28, P 0.032), patients ≤ 45 years of age (OR 1.12, 95% CI 1.02-1.24, P 0.022), black patients (OR 1.26, 95% CI 1.04-1.53, P 0.019), and medicare insured patients (OR 1.37, 95% CI 1.20-1.57, P < 0.001) were associated with failure to receive RAI according to guidelines. Treatment at academic (OR 0.58 95% CI 0.48-0.69, P < 0.001) or comprehensive cancer centers (OR 0.63, 95% CI 0.53-0.76, P < 0.001) were associated with compliant delivery of RAI therapy. 896 (22.8%) patients received RAI when not recommended, and Medicare insurance (OR 0.62, 95% CI 0.48-0.80, P < 0.001) and comprehensive cancer centers (OR 1.41, 95% CI 1.01-1.98, P 0.045) were associated with guideline nonconcordant RAI delivery in this group. Income and education had no impact on nonguideline treatment. Conclusions: Female gender, age ≤ 45, medicare insurance, race, and hospital category are associated with nonguideline treatment for PTC. Increased awareness of these patient categories is needed to improve compliance with treatment guidelines
Superoxide and hydrogen peroxide counterregulate myogenic contractions in renal afferent arterioles from a mouse model of chronic kidney disease
Authors: Lingli Li, En Yin Lai, Zaiming Luo, Glenn Solis, Kathy K. Griendling, W. Robert Taylor, Pedro A. Jose, Anton Wellsten, William J. Welch, Christopher S. Wilcox
Journal: Kidney International (2017)