tbuckley/cabot-search huggingface dataset:
Canine model for the study of intraepithelial lesions (IELs) associated with human breast cancer: histopathological study
Authors: Sulma I. Mohammed
Journal: Cancer Research (2005)

1081  PURPOSE: Intraepithelial lesions (IELs) including hyperplasia, dysplasia, and carcinoma in situ are thought to be premalignant lesions and have been recognised as risk factors for invasive breast cancer in humans. Reducing the burden of breast IEL through intervention is believed to result in a decreased burden of invasive cancer. Rapid evolution of chemopreventative agents may reduce breast cancer risk. An animal model that develops spontaneous IEL similar to human IEL is needed to test different prevention modalities prior to human clinical trials. The purpose of this study is to characterize the canine IEL that occurs spontaneously in canine mammary tumors and compared its histopathology to those that occur in humans. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded mammary biopsy specimens from 123 female dogs with spontaneous mammary tumors were retrieved from the archives of the Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital, Purdue University. All tumors were classified histologically according to the WHO International Histologic Classification of Tumors of Domestic Animals. Histologic sections were also evaluated for the presence of mammary hyperplasia, dysplasia, or intraepithelial neoplasia. The distinction between atypical hyperplasia and ductal carcinoma in situ was made using size (in millimetres and/or number of ducts involved), and morphological criteria (cytologic and architectural features). RESULTS: IELs morphologically identical to human breast disease were identified in 50 of 123 female dogs with mammary neoplasia. The lesions identified included those not associated with significant increased risk [such as intraductal papilloma (3), adenosis (blunt duct adenosis)(7), sclerosing adenosis (4), Sclerotic papilloma (1), and fibroadenoma (1)] to those associated with intermediate risk [moderate epithelial ductal hyperplasia (papillomatosis) (7)] to those associated with high risk of developing invasive cancer [atypical ductal hyperplasia (ADH) (3), and Ductal carcinoma in situ (DCIS) (22)]. In 21/22 DCIS and in 3/3 ADH lesions were associated with histologically malignant mammary tumors. In addition, one case each of atypical papilloma, and fibroadenoma with high cellularity/ phylloides tumor were observed. CONCLUSION: Canine pre-neoplastic lesions show cytological and architectural features identical to their human breast counterparts. The similarity between canine and human IELs and their association with invasive carcinoma suggest that the canine mammary gland may be a useful model for studying carcinogenesis, cancer progression, treatment, and prevention. The U.S. Army Medical Research and Materiel Command under W81WXH-04-1-0196 supported this work
The L-arginine transporter, solute carrier 7a2, promotes intestinal tumorigenesis independently of NO production by the inducible NO synthase
Authors: Natalie Dorwin, Joy Hardison, Jin Mo Park, Carol L. Macleod, Lesley G. Ellies
Journal: Cancer Research (2005)

4687  The role of the L-arginine/nitric oxide (NO) pathway in intestinal tumorigenesis remains controversial despite numerous studies. The L-arginine transporter solute carrier 7a2 (Slc7a2), also known as the cationic amino acid transporter-2 (CAT-2) supplies L-arginine for NO production by the inducible NO synthase (iNOS) in macrophages and is coordinately up-regulated with iNOS in models of inflammatory disease. We have determined the effects of Slc7a2 and iNOS gene ablation on intestinal tumorigenesis in the Apc (Min/+) model of familial adenomatous polyposis coli. Min/+Slc7a2-/- mice developed significantly fewer intestinal polyps that were smaller in size than wild type controls (Min/+Wt). By contrast, the loss of iNOS resulted in a significant increase in the number and size of Min/+iNOS-/- intestinal polyps. Realtime PCR revealed a 15-20 fold higher level of iNOS expression in normal small intestine of Min/+ mice compared with polyps in the same region and a lack of coordinate regulation between iNOS and Slc7a2. Loss of Slc7a2 reduced iNOS expression to approximately half the normal levels. Expression of iNOS was very low in both normal colon and colon polyps, suggesting that NO production by infiltrating macrophages present in all genotypes, is not a feature of Min/+ intestinal tumorigenesis. Intestinal polyps showed a slight increase in Slc7a2 expression compared with normal tissues. Neither Slc7a2 nor iNOS deficiency impacted COX-2 or arginase I expression, both of which were low in normal intestine and high in intestinal polyps. Our results indicate that Slc7a2 can modulate iNOS expression in intestinal epithelium and suggest that cationic amino acid transport is involved in the promotion of Min/+ tumorigenesis via NO-independent mechanisms. Thus, Slc7a2 and iNOS are not linked in NO production in the intestinal epithelium. The antineoplastic properties of NO production by iNOS in the Min/+ model may be related to its importance in protecting the gut from microbial pathogens, thereby reducing inflammation. These results may help to explain why NO-donating nonsteroidal antiinflammatory drugs (NSAIDs) are more effective than traditional NSAIDS in preventing colorectal cancer.
Abstract 17857: Doxycycline Prevents Interleukin-1 Induced Left Ventricular Systolic Dysfunction in the Mouse
Authors: Eleonora Mezzaroma, Stefano Toldo, Benjamin W Van Tassell, Antonio Abbate
Journal: Circulation (2012)

Background: Interleukin-1 (IL-1) impairs myocardial contractility. We hypothesized that activation of MMP-2 in the heart following IL-1 leads to degradation of Troponin I and subsequent impaired co...
Lower back pain and bladder dysfunction
Authors: Aernout R J Langeveld, Johannes L Bron, Annemieke J E de Bruijn
Journal: BMJ (2008)

A 36 year old man presented with progressive low back pain and bladder dysfunction. He had had periods of non-specific back pain for more than a year. In the past two weeks the pain had got worse, radiating from the left dorsolateral thigh to the lateral site of his left foot. For three days he had had difficulties initiating micturation, and the flow had weakened. He felt numb sensations in the left scrotum, the perineal region, and on the lateral site of the left foot. He also noticed muscle weakness in the left foot. He had no history of trauma or recent disease.

General physical examination indicated a healthy young man. Neurological examination showed paralysis of the left foot extensors, motor weakness of left foot flexors (grade 2-3), and sensory deficits from the medial leg to the dorsal lateral foot. The patellar reflexes were vivid on both sides (left more than right). The ankle jerk was absent on both sides and plantar flexes indifferent. Rectal examination indicated saw saddle anaesthesia and low sphincter tone. Normal and crossed …
Correction to: Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis
Authors: Yu-Shui Ma, Tao Huang, Xiao-Ming Zhong, Hong-Wei Zhang, Xian-Ling Cong, Hong Xu, Gai-Xia Lu, Fei Yu, Shao-Bo Xue, Zhong-Wei Lv, Da Fu
Journal: Molecular Cancer (2019)

Following publication of the original article [1], the authors reported an error in affiliation 5.
Maternal Comorbidities and Complications of Delivery in Pregnant Women With Congenital Heart Disease
Authors: Lauren E. Schlichting, Tabassum Z. Insaf, Ali N. Zaidi, George K. Lui, Alissa R. Van Zutphen
Journal: Journal of the American College of Cardiology (2019)

Pregnant women with congenital heart defects (CHDs) may be at increased risk for adverse events during delivery. This study sought to compare comorbidities and adverse cardiovascular, obstetric, and fetal events during delivery between pregnant women with and without CHDs in the United States. Comorbidities and adverse delivery events in women with and without CHDs were compared in 22,881,691 deliveries identified in the 2008 to 2013 National Inpatient Sample using multivariable logistic regression. Among those with CHDs, associations by CHD severity and presence of pulmonary hypertension (PH) were examined. There were 17,729 deliveries to women with CHDs (77.5 of 100,000 deliveries). These women had longer lengths of stay and higher total charges than women without CHDs. They had greater odds of comorbidities, including PH (adjusted odds ratio [aOR]: 193.8; 95% confidence interval [CI]: 157.7 to 238.0), congestive heart failure (aOR: 49.1; 95% CI: 37.4 to 64.3), and coronary artery disease (aOR: 31.7; 95% CI: 21.4 to 47.0). Greater odds of adverse events were observed, including heart failure (aOR: 22.6; 95% CI: 20.5 to 37.3), arrhythmias (aOR: 12.4; 95% CI: 11.0 to 14.0), thromboembolic events (aOR: 2.4; 95% CI: 2.0 to 2.9), pre-eclampsia (aOR: 1.5; 95% CI: 1.3 to 1.7), and placenta previa (aOR: 1.5; 95% CI: 1.2 to 1.8). Cesarean section, induction, and operative vaginal delivery were more common, whereas fetal distress was less common. Among adverse events in women with CHDs, PH was associated with heart failure, hypertension in pregnancy, pre-eclampsia, and pre-term delivery; there were no differences in most adverse events by CHD severity. Pregnant women with CHDs were more likely to have comorbidities and experience adverse events during delivery. These women require additional monitoring and care.
Picture quiz: Oral white patches
Authors: Amy Ford
Journal: BMJ (2004)

A 46 year old woman presented to her general practitioner with a history of painful oral ulcers. On examination of her mouth, her doctor saw a white patch on the floor of her mouth (fig). The general practitioner referred her to the local oral medicine department for further investigation and treatment. She was taking no drugs. She smoked 25-30 cigarettes a day and drank 20-22 units of alcohol a week.

1.  What does the figure show?

2.  What is the differential diagnosis?

3.  How could you reach a definitive diagnosis?

1.  The figure shows the front view of the mouth with the tongue raised. On the ventral (top) aspect of the tongue, you can see a diffuse white lesion which is slightly raised from the rest of the oral mucosa.

2.  You can group white patches in a number of ways. Clinically, they can be separated depending on whether the lesion can be wiped away or not. In general, lesions which can be wiped away are due to accumulation of epithelial debris or inflammatory exudates. Lesions which cannot be …
New doctors benefit from induction scheme
Authors: Michael Roberts
Journal: BMJ (2004)

Newly qualified doctors are more confident and clinically competent at work if given an initial induction period into their jobs (Med Educ 2004;38:998- 1001). Research has suggested that preregistration house officers (PRHOs) feel ill equipped when they first start working. Michael Roberts, professor of medical education for clinical practice at Queen Mary and Westfield, Barts, and the London Medical Schools, explained,

My personal observation was of struggling new PRHOs who were mainly coming to me as their …
Facing the future
Authors: Marissa See
Journal: BMJ (2001)

James Partridge is not a man to shy away from publicity. In fact, he welcomes it because publicity equals exposure and exposure equals awareness. James is the founder and director of the charity Changing Faces, which aims to provide direct help to those with facial disfigurements and promote awareness in those without them.

Thirty years ago, at the age of 18, the Land Rover he was driving overturned and caught fire. That completely changed his life. “I don't encourage you to go into fire,” he said, as if to dispel any notions I might have been toying with. “There is no air in fire. To get out of it is to feel quite liberated. Glad you survived.” The other passengers escaped with relatively minor injuries.

James suffered severe facial and body burns. “After about three months, I looked at myself in the mirror for the first time. And what I saw was something different from what I was expecting to see,” he said. “Very, very different face, and 40% burns.”

James believes that there are two …
Abstract P2-08-29: The impact of time interval between diagnosis and surgery in each type and stage of breast cancer
Authors: J-M Kim, HJ Choi, I Kim, JM Ryu, J Yu, JE Lee, SW Kim, SJ Nam, SK Lee
Journal: Cancer Research (2019)

Abstract Background: There are many factors that might contribute to the delay of surgery in patients with breast cancer. Previous studies investigate the influence of delay of surgery, but they reported inconsistent results. The purpose of this study was to evaluate the impact of time of surgery on prognosis of breast cancer. Methods: We performed a retrospective review of the patients with breast cancer, who received surgery between 1992 and 2009, by using data from Korea Breast Cancer Society Registry. Kaplan-Meier survival analysis and Cox regression model were used to evaluate the impact of time to surgery in breast cancer and subgroup analyses were performed for each disease stage and molecular subtype. Result: A total 14727 patients were included for analysis. Delay of surgery more than 31 days was associated with worse survival for breast cancer [hazard ratio (HR) = 2.16; 95% confidence interval (CI), 1.936-2.408, p&amp;lt;0.001]. Subgroup analyses revealed that over 31 days of surgical delay were significantly associated with worse survival in hormone receptor positive and HER-2 negative (p&amp;lt;0.001), hormone receptor positive and HER-2 positive (p&amp;lt;0.001), hormone receptor negative and HER-2 positive (p&amp;lt;0.001), triple negative (p&amp;lt;0.001) and stage II, III breast cancer patients (p&amp;lt;0.001). Conclusion: Surgical delay of more than 31 days were independent risk factors for worse outcome of breast cancer in each molecular subtype and breast cancer group except stage 0 and I. Although preoperative evaluation is required, surgical delay should be shortened to enhance survival of breast cancer, especially in patients with tumor size more than 2cm or presence of lymph node metastasis. Citation Format: Kim J-M, Choi HJ, Kim I, Ryu JM, Yu J, Lee JE, Kim SW, Nam SJ, Lee SK. The impact of time interval between diagnosis and surgery in each type and stage of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-29.
Methionine is a metabolic dependency of tumor-initiating cells
Authors: Zhenxun Wang, Lian Yee Yip, Jia Hui Jane Lee, Zhengwei Wu, Hui Yi Chew, Pooi Kiat William Chong, Chin Chye Teo, Heather Yin-Kuan Ang, Kai Lay Esther Peh, Ju Yuan, Siming Ma, Li Shi Kimberly Choo, Nurhidayah Basri, Xia Jiang, Qiang Yu, Axel M. Hillmer, Wan Teck Lim, Tony Kiat Hon Lim, Angela Takano, Eng Huat Tan, Daniel Shao Weng Tan, Ying Swan Ho, Bing Lim, Wai Leong Tam
Journal: Nature Medicine (2019)
Abstract MP49: Racial/Ethnic Differences in Receipt of Follow-up Care and Type 2 Diabetes Diagnosis Following Gestational Diabetes
Authors: Julie K Bower, Brittney Francis, Seuli Bose-Brill, Christina L Wassel
Journal: Circulation (2018)

Introduction: Gestational diabetes mellitus (GDM) affects up to 14% of pregnancies in the U.S. and is associated with a sevenfold increased lifetime risk for type 2 diabetes (T2D). Clinical guidelines recommend postpartum glucose screening 4-12 weeks after a GDM pregnancy, and re-screening every 1-3 years thereafter. However, an inadequate proportion of persons with GDM actually receive these screenings. Racial/ethnic differences in risk of developing T2D following GDM may partially be driven by differential receipt of screening services. The aim of this study was to examine racial/ethnic differences in subsequent development of T2D, receipt of screening services, and glycated hemoglobin (HbA1c) in a nationally representative sample of women with a GDM history. Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES, 2007-2014). Race/ethnicity, GDM and diabetes diagnosis, and receipt of diabetes screening tests were determined by self-report; HbA1c was measured using standard laboratory procedures. Associations of race/ethnicity with outcomes of interest were evaluated using linear, logistic, and Cox regression, with adjustment for demographic, clinical, and healthcare access factors. Results: Among 629 women with a history of GDM in NHANES, non-Hispanic Black women had 98% higher risk (95% CI (1.28, 3.08), p=0.003), and Hispanics about double the risk (HR = 2.04, 95% CI (1.25, 3.32), p=0.005) of developing T2D following GDM compared to non-Hispanic Whites. In fully adjusted models, this was attenuated slightly, although still statistically significantly greater risk for both non-Hispanic Black (p=0.05) and Hispanic (p=0.03) women. Both non-Hispanic Black and Hispanic women were less likely to report being screened for diabetes in the past 3 years. In adjusted linear regression models, among women who remained diabetes-free, non-Hispanic Blacks had 0.40-% point higher HbA1c (p=0.02), and Hispanics had 0.26-% point higher HbA1c (p&lt;0.001) compared to non-Hispanic Whites. Additionally, the odds of prediabetes were 4.9-fold higher for non-Hispanic Blacks (p&lt;0.001), and 2.4-fold greater for Hispanics (p=0.03) as compared to non-Hispanic Whites. Odds of undiagnosed diabetes (HbA1c&gt;6.5%) were significantly higher in non-Hispanic Blacks (OR=3.3, p=0.05) and marginally greater in Hispanics (OR=3.5, p=0.07) compared to non-Hispanic Whites. Conclusions: Differential receipt of follow-up services by minority women may exacerbate observed disparities in the burden of T2D. In this study, racial/ethnic disparities were apparent with regards to T2D diagnosis, receipt of diabetes screening tests, and HbA1c. Additional investigation to identify underlying factors contributing to this observed disparity will be particularly important to inform recommendations to improve delivery of quality care equitably across population subgroups.
Aurora A Inhibition Eliminates Myeloid Cell–Mediated Immunosuppression and Enhances the Efficacy of Anti–PD-L1 Therapy in Breast Cancer
Authors: Tingting Yin, Zhi-Bin Zhao, Jing Guo, Tianchen Wang, Jing-Bo Yang, Chao Wang, Jie Long, Shisong Ma, Qiang Huang, Kaiguang Zhang, Xiaopeng Ma, Chenhai Liu, Suling Liu, Zhe-Xiong Lian, Zhenye Yang
Journal: Cancer Research (2019)

The Aurora A inhibitor alisertib shows encouraging activities in clinical trials against advanced breast cancer. However, it remains unclear whether and how the inflammatory microenvironment is involved in its efficacy. Here, we demonstrated that inhibition of Aurora A directly reshaped the immune microenvironment through removal of tumor-promoting myeloid cells and enrichment of anticancer T lymphocytes, which established a tumor-suppressive microenvironment and significantly contributed to the regression of murine mammary tumors. Mechanistically, alisertib treatment triggered apoptosis in myeloid-derived suppressor cells (MDSC) and macrophages, resulting in their elimination from tumors. Furthermore, alisertib treatment disrupted the immunosuppressive functions of MDSC by inhibiting Stat3-mediated ROS production. These alterations led to significant increases of active CD8+ and CD4+ T lymphocytes, which efficiently inhibited the proliferation of tumor cells. Intriguingly, alisertib combined with PD-L1 blockade showed synergistic efficacy in the treatment of mammary tumors. These results detail the effects of Aurora A inhibition on the immune microenvironment and provide a novel chemo-immunotherapy strategy for advanced breast cancers. SIGNIFICANCE: These findings show that inhibition of Aurora A facilitates an anticancer immune microenvironment, which can suppress tumor progression and enhance anti-PD-L1 therapy in breast cancer.See related commentary by Rivoltini et al., p. 3169.
Viewpoint: Good doctors teach us about life
Authors: Teresa Pun
Journal: BMJ (2007)

We are surrounded by mentors, but the ones who have had the most impact on my path to becoming a physician are the ones who taught me something other than just the traditional diagnosis and treatment side of medicine.



I recently spent a day at the Hospital for Sick Children to see a “whack of tonsils,” as recommended by one of the paediatric otolaryngologists. There were six scheduled tonsil and adenoid surgeries, but after the fifth consecutive one, I was getting bored. I wandered into the residents' lounge for a coffee and found …
Biphosphonate Therapy, Risk of Fracture, and Sites of Bone Mineral Density Assessments in Kidney Transplantation
Authors: Nahid Tabibzadeh, Nathalie Chavarot, Martin Flamant, Emmanuelle Vidal-Petiot
Journal: Journal of the American Society of Nephrology (2019)

We read with great interest “A randomized trial of zoledronic acid to prevent bone loss in the first year after kidney transplantation” by Marques et al.1 This study suggests that bisphosphonates are safe and probably beneficial in preventing the risk of fractures in kidney transplant recipients. This is all the more important, because this population, as outlined by the authors, rarely benefits from these drugs despite their proven efficiency in preventing fracture incidence, especially in patients receiving corticosteroid therapy. Therefore, this article highlights that the fear of adynamic bone disease should not lead clinicians to treat patients with kidney transplants different from the general population. Noteworthy, the increase in bone mineral density observed in both groups in this study is in line with the results of a recent observational study conducted in 355 kidney transplant recipients that showed an improvement in hip and vertebral bone mineral density assessed by dual energy x-ray absorptiometry (DXA) at 2 years post-transplantation, improvement that was significantly higher in patients receiving bisphosphonates (n=95; 26% of patients). Broader clinical trials are thus warranted to determine whether the findings of Marques et al.1 can be extrapolated to patients at higher risk of bone mineral disorder. Indeed, as acknowledged by the authors, patients were young, had a relatively short time on dialysis before living donor transplantation, and had a prevalence of osteoporosis of <20%, less than that found in the study by Segaud et al.2 (40.9% osteoporosis and 42.8% osteopenia). The authors showed interesting results of peripheral bone assessment by high-resolution peripheral quantitative computed tomography (HR-pQCT) and emphasized the importance of peripheral bone changes. Although this clinical research tool enables microarchitecture evaluation, it is not routinely available. It would have been of major interest to compare HR-pQCT with forearm bone mineral density assessed by DXA. Indeed, Iyer et al.3 showed a radial bone mineral density decrease at 12 months by DXA as well as by HR-pQCT along with microarchitectural changes, but they showed no significant changes in other sites. In the same line, in a large Danish cohort, Hansen et al.4 showed an increased prevalence of forearm fractures in patients with kidney transplants compared with the general population and compared with patients on dialysis. Whether HR-pQCT is superior to DXA for evaluation of bone strength and prediction of fractures remains to be evaluated. Taken together, these considerations stress the need for peripheral bone mineral density evaluation in kidney transplant recipients to guide appropriate treatment and follow-up. Disclosures None.