bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon Regulatory Factor 4 Inhibits Neointima Formation by Engaging Krüppel-Like Factor 4 Signaling
Authors: Cheng Wen-Lin , She Zhi-Gang , Qin Juan-Juan , Guo Jun-Hong , Gong Fu-Han , Zhang Peng , Fang Chun , Tian Song , Zhu Xue-Yong , Gong Jun , Wang Zhi-Hua , Huang Zan , Li Hongliang 
Published: August 2017

Background:
The mechanisms underlying neointima formation remain unclear. Interferon regulatory factors (IRFs), which are key innate immune regulators, play important roles in cardiometabolic diseases. However, the function of IRF4 in arterial restenosis is unknown.

Methods:
IRF4 expression was first detected in human and mouse restenotic arteries. Then, the effects of IRF4 on neointima formation were evaluated with universal IRF4-deficient mouse and rat carotid artery injury models. We performed immunostaining to identify IRF4-expressing cells in the lesions. Smooth muscle cell (SMC)–specific IRF4-knockout (KO) and -transgenic (TG) mice were generated to evaluate the effects of SMC-IRF4 on neointima formation. We used microarray, bioinformatics analysis, and chromatin immunoprecipitation assay to identify the downstream signals of IRF4 and to verify the targets in vitro. We compared SMC-IRF4-KO/Krüppel-like factor 4 (KLF4)–TG mice with SMC-IRF4-KO mice and SMC-specific IRF4-TG/KLF4-KO mice with SMC-specific IRF4-TG mice to investigate whether the effect of IRF4 on neointima formation is KLF4-dependent. The effect of IRF4 on SMC phenotype switching was also evaluated.

Results:
IRF4 expression in both the human and mouse restenotic arteries is eventually downregulated. Universal IRF4 ablation potentiates neointima formation in both mice and rats. Immunostaining indicated that IRF4 was expressed primarily in SMCs in restenotic arteries. After injury, SMC-IRF4-KO mice developed a thicker neointima than control mice. This change was accompanied by increased SMC proliferation and migration. However, SMC-specific IRF4-TG mice exhibited the opposite phenotype, demonstrating that IRF4 exerts protective effects against neointima formation. The mechanistic study indicated that IRF4 promotes KLF4 expression by directly binding to its promoter. Genetic overexpression of KLF4 in SMCs largely reversed the neointima-promoting effect of IRF4 ablation, whereas ablation of KLF4 abolished the protective function of IRF4, indicating that the protective effects of IRF4 against neointima formation are KLF4-dependent. In addition, IRF4 promoted SMC dedifferentiation.

Conclusions:
IRF4 protects arteries against neointima formation by promoting the expression of KLF4 by directly binding to its promoter. Our findings suggest that this previously undiscovered IRF4-KLF4 axis plays a key role in vasculoproliferative pathology and may be a promising therapeutic target for the treatment of arterial restenosis.
Exploring Coronary Circulatory Response to Stenosis and Its Association With Invasive Physiologic Indexes Using Absolute Myocardial Blood Flow and Coronary Pressure
Authors: Lee Joo Myung , Hwang Doyeon , Park Jonghanne , Zhang Jinlong , Tong Yaliang , Kim Chee Hae , Bang Ji-In , Suh Minseok , Paeng Jin Chul , Cheon Gi Jeong , Koo Bon-Kwon 
Published: August 2017

Background:
Although invasive physiological assessment for coronary stenosis has become a standard practice to guide treatment strategy, coronary circulatory response and changes in invasive physiological indexes, according to different anatomic and hemodynamic lesion severity, have not been fully demonstrated in patients with coronary artery disease.

Methods:

One hundred fifteen patients with left anterior descending artery stenosis who underwent both
13
N-ammonia positron emission tomography and invasive physiological measurement were analyzed. Myocardial blood flow (MBF) measured with positron emission tomography and invasively measured coronary pressures were used to calculate microvascular resistance and stenosis resistance.

Results:

With progressive worsening of angiographic stenosis severity, both resting and hyperemic transstenotic pressure gradient and stenosis resistance increased (
P
<0.001 for all) and hyperemic MBF (
P
<0.001) and resting microvascular resistance (
P
=0.012) decreased. Resting MBF (
P
=0.383) and hyperemic microvascular resistance (
P
=0.431) were not changed and maintained stable. Both fractional flow reserve and instantaneous wave-free ratio decreased as angiographic stenosis severity, stenosis resistance, and transstenotic pressure gradient increased and hyperemic MBF decreased (all
P
<0.001). When the presence of myocardial ischemia was defined by both low hyperemic MBF and low coronary flow reserve, the diagnostic accuracy of fractional flow reserve and instantaneous wave-free ratio did not differ, regardless of cutoff values of hyperemic MBF and coronary flow reserve.

Conclusions:

This study demonstrated how the coronary circulation changes in response to increasing coronary stenosis severity using
13
N-ammonium positron emission tomography–derived MBF and invasively measured pressure data. Currently used resting and hyperemic pressure–derived invasive physiological indexes have similar patterns of relationships to the different anatomic and hemodynamic lesion severities.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01366404.
Prognostic Indicators in Differentiated Thyroid Carcinoma
Authors: Dean Diana S. , Hay Ian D. 
Published: August 2017

Background Thyroid cancer ranges from well-differentiated lesions with an excellent prognosis to anaplastic carcinoma, which is almost uniformly fatal. Thus, methods to assess the behavior of thyroid malignancies are necessary to arrive at appropriate treatment decisions. Methods We discuss the factors that affect the prognosis of patients with well-differentiated thyroid malignancies, including papillary, follicular, Hürthle cell, and medullary thyroid carcinomas. We also review the presentation, therapy, and outcome of patients seen at our center over a span of 50 years. These data have identified those prognostic factors that are predictive of survival and recurrence in differentiated thyroid cancer. Results Several classifications with different variables have been developed to define risk-group categories. Three widely used systems, in addition to the TNM staging system, include AGES, AMES, and MACIS. Conclusions A better understanding of independently important prognostic variables will result in improved patient care and treatment.
Bladder-Sparing Treatment of Invasive Bladder Cancer
Authors: Rivera Inoel , Wajsman Zev 
Published: August 2017

Background Radical cystectomy with pelvic lymph node dissection is the standard treatment for patients with invasive bladder cancer. However, many alternative techniques to spare the bladder have been investigated. Methods We review the experience reported in the literature on bladder-sparing techniques, including transurethral resection, chemotherapy, and radiation for muscle-invasive disease. Results Most comparative studies indicate that local recurrence and survival outcomes for bladder-sparing approaches are inferior to those from radical cystectomy to control muscle-invasive bladder cancer. Conclusions Although molecular biologic techniques may have the capacity to identify a subgroup who may benefit from a bladder-sparing approach, cystectomy is normally required for optimal results.
Prostate Cancer: Screening and Early Detection
Authors: Cookson Michael S. 
Published: August 2017

Background Despite more than a decade of prostate-specific antigen (PSA)-based screening, the proven impact of screening on mortality due to prostate cancer continues to be controversial. Methods A literature review of issues pertaining to the epidemiology, screening, early detection, and mortality as they relate to prostate cancer was conducted. Included in the review are PSA refinements, controversies of screening, and organization guidelines. Finally, recent reports of mortality rates in the post-PSA era are presented for discussion. Results Prostate cancer mortality rates have begun to decline for the first time since statistics have been recorded. The recent decline in age-adjusted mortality rates from prostate cancer is significant, and this decline appears to be earlier than would have been predicted. This finding, coupled with the dramatic decline in metastatic disease, implies that PSA-based screening may be responsible for a significant portion of this improvement in mortality. Conclusions The cost of prostate cancer screening appears to be acceptable. Randomized studies of PSA-based screening are currently ongoing, although the results may not be available for a decade. Currently, the best evidence is derived from population-based studies that appear to show a benefit to prostate cancer screening.
Breast Cancer Sentinel Node Metastases: Histopathologic Detection and Clinical Significance
Authors: Ollila David W. , Stitzenberg Karyn B. 
Published: August 2017

BackgroundLymphatic mapping with sentinel lymphadenectomy (LM/SL) is an accurate and less morbid means of determining the tumor status of the axilla in breast cancer patients than standard level I and II axillary lymph node dissection (ALND). This review addresses the handling and pathologic examination of the sentinel node (SN), the clinical significance of tumor within the SN, and the risk factors for non-SN tumor involvement.MethodsThe seminal works that have addressed pathologic examination of ALND specimens and SN specimens are summarized, and the important studies attempting to identify predictors of non-SN metastases in patients with a tumor-involved SN are reviewed.ResultsStandard single-section hematoxylineosin (H&E) examination is inadequate for reliable detection of axillary or SN metastases. Large studies appropriately powered to detect a survival difference for patients with micrometastatic disease are reviewed. The current data on the clinical significance of micrometastatic nodal disease is inconclusive. While several strong predictors of non-SN tumor involvement have been identified, none is reliable enough to allow omission of ALND in patients with a tumor-involved SN.ConclusionsRoutine examination of the SN specimen should include serial sections with H&E stain. Ongoing prospective clinical trials should help to define the clinical significance of SN micrometastases. Furthermore, these trials could help identify predictors of non-SN metastasis that would allow a subset of patients with a tumor-involved SN to avoid the morbidity of ALND.
Management of Breast Cancer in the Older Woman
Authors: Balducci Lodovico , Extermann Martine , Carreca Ignazio 
Published: August 2017

Background Approximately half of all breast cancer cases occur after age 65. Several aspects for the treatment of early breast cancer may be influenced by patient age, including postoperative irradiation after partial mastectomy, axillary lymphadenectomy, primary medical treatment of early breast cancer, and adjuvant chemotherapy. Methods The authors review the literature regarding age-specific issues in the management of breast cancer, and they report their own experience in treating older women with breast cancer. Results In terms of survival and disease-free survival, tamoxifen alone in primary breast cancer is inferior to surgical treatment followed by adjuvant tamoxifen. Tamoxifen alone should be reserved for patients with absolute contraindications to mastectomy. Adjuvant chemotherapy is beneficial to women with hormone receptor-poor tumors. In those with hormone receptor-rich tumors, adjuvant chemotherapy is beneficial for HER2-positive tumors, and the regimen should contain an anthracycline. Conclusions Although the risk of local recurrence after partial mastectomy declines with increasing age, the decision to forego radiation therapy is individualized based on risk of recurrence and on patient desires and resources. The advent of lymph node mapping obviates the need for lymphadenectomy in most patients. The benefits and risks of adjuvant chemotherapy should be individually assessed according to tumor stage, life expectancy, comorbidity, and expected tolerance of treatment.
External-Beam Radiotherapy in the Management of Carcinoma of the Prostate
Authors: Zlotecki Robert A. 
Published: August 2017

Background External-beam radiotherapy (EBRT) has been used in the treatment of adenocarcinoma of the prostate gland for more than 30 years. Well-documented clinical series have demonstrated the effectiveness of EBRT in achieving both cause-specific survival and freedom from biochemical (prostate-specific antigen [PSA]) progression. Methods The indications and expected treatment results for treatment by EBRT in the management of adenocarcinoma of the prostate gland are reviewed. The treatment of early-stage disease definitively by EBRT alone or as complement to radioactive seed implant is emphasized. In the management of locally advanced disease, the use of EBRT with combined androgen ablation is discussed as definitive therapy and also as indicated in the postoperative adjuvant management of surgically identified pathologic stage T3 disease. Results The relative clinical benefit of EBRT compared with the mostly predictable and well-defined moderate side effects, which are manageable in most instances by conservative measures treatment, is well established. Advances in defining radiation-beam parameters have led to more effective and safer treatment for prostate cancer. Conclusions EBRT has historically been a mainstay in the management of prostate cancer. It remains a useful and indicated treatment modality in patients with early-stage, locally advanced, and metastatic disease.
Transoral Laser Microsurgery in Carcinomas of the Oral Cavity, Pharynx, and Larynx
Authors: Werner Jochen A. , Dünne Anja A. , Folz Benedikt J. , Lippert Burkard M. 
Published: August 2017

Background Since the introduction of laser technology in the 1960s, use of the technique in treating laryngeal diseases has demonstrated several advantages over conventional resections in selected cases. Methods The authors review the published data on oncologic laser surgery for the treatment of head and neck carcinomas, and they also describe their own clinical experience with transoral laser surgery for the treatment of carcinomas of the oral cavity, pharynx, and larynx. Results Laser surgery has achieved a key position in minimally invasive treatment concepts in the ears, nose, and throat area, especially for the treatment of malignancies of the upper aerodigestive tract. The CO2 laser is the approach most commonly used. Conclusions New and improved applications of laser therapy in the treatment of cancer are being explored. As more surgeons become experienced in the use of lasers and as our knowledge of the capabilities and advantages of this tool expands, lasers may play a larger role in the management of head and neck cancers.
Clinical Considerations in the Management of Individuals at Risk for Hereditary Breast and Ovarian Cancer
Authors: Robson Mark E. 
Published: August 2017

Background Hereditary predisposition to breast and ovarian cancer, most commonly due to germline mutations in BRCA1 and BRCA2, has been recognized for many years. The optimal clinical management of individuals with such a predisposition is not yet completely defined. Methods The current literature regarding the clinical management of individuals at risk for hereditary breast and ovarian cancer was reviewed. Results Women with germline BRCA1 or BRCA2 mutations are at substantially increased risk for breast and ovarian cancer, although the risks may not be as high as originally reported. Current surveillance options are restricted in their effectiveness by both host and tumor factors as well as limitations of the techniques. Surgical prevention options, while effective, may be complicated by physical or psychological morbidity. Nonsurgical prevention options are under development. Conclusions The ability to define women as being at hereditary risk for breast and ovarian cancer facilitates the use of specialized surveillance and prevention strategies. Genetic testing, which plays a role in defining risk, requires careful pre- and post-test counseling to discuss the limitations of testing itself and available management strategies.
Aromatase Inhibitors in Breast Cancer: An Update
Authors: Lake Diana E. , Hudis Clifford 
Published: August 2017

Background Tamoxifen has been the endocrine treatment of choice for patients with breast cancer. The development of selective aromatase inhibitors has offered an alternative management approach for patients in whom a hormonal approach is indicated. Methods The authors reviewed reports in which aromatase inhibitors were compared with tamoxifen for the treatment of metastatic disease, as well as information pertinent to their use as adjuvant therapy. Results Both nonsteroidal (anastrozole and letrozole) and steroidal (exemestane) aromatase inhibitors for metastatic disease appear to provide superior efficacy and a better toxicity profile in first- and second-line treatment of metastatic disease than tamoxifen. Early results from the ATAC trial suggest anastrozole is superior to tamoxifen for disease-free survival, particularly in receptor-positive patients, and in reducing the incidence of contralateral breast cancer. Conclusions Aromatase inhibitors have important roles in optimal management of postmenopausal patients with hormone-responsive metastases in both the adjuvant and advanced-disease settings.
Cancer Genetics Knowledge and Beliefs and Receipt of Results in Ashkenazi Jewish Individuals Receiving Counseling for BRCA1/2 Mutations
Authors: Kelly Kimberly , Leventhal Howard , Marvin Monica , Toppmeyer Deborah , Baran Jill , Schwalb Marvin 
Published: August 2017

Background Genetic counseling for BRCA1 and BRCA2 mutations (mutations associated with increased risk of breast-ovarian cancer) endeavors to communicate information that will help individuals make informed decisions regarding genetic testing. Methods This repeated-measures study examined cancer genetics knowledge and beliefs before and after counseling and their relationship to receipt of results for BRCA1/2 mutations in 120 highly educated Ashkenazi Jewish individuals. Results A repeated-measures analysis examined change in knowledge and beliefs regarding personal behavior, mechanisms of cancer inheritance, meaning of a positive result, practitioner knowledge, frequency of inherited cancer, and meaning of a negative result from pre- to post-counseling with the between subjects variables of education (with/without graduate training) and personal history of breast or ovarian cancer (yes/no), and risk of having a mutation entered as a covariate. Mechanisms of cancer inheritance, meaning of a positive result, and practitioner knowledge increased from pre- to post-counseling. Those with graduate training had higher ratings of mechanisms of cancer inheritance ratings and lower ratings of frequency of inherited cancers than those without. Mann-Whitney U tests found those testing had higher ratings in mechanisms of cancer inheritance, specifically in the association of multiple primary cancers with hereditary cancer, than those not testing. Conclusions Genetic counseling is helpful in improving overall knowledge of cancer genetics even for highly educated individuals. Particular areas of knowledge improvement should be explored in relation to receipt of results, especially to further elucidate the relationship of knowledge of the association of multiple primary cancers with hereditary cancer to receipt of test results.
Newer Imaging Modalities to Assess Tumor in the Prostate
Authors: Hersh Marla R. , Knapp Edson L. , Choi Junsung 
Published: August 2017

Background Several advances in the imaging of prostate cancer have been made in recent years. Diagnostic staging has become increasingly complex and confusing as newer technologies have developed more rapidly than research has been able to confirm or refute the accuracy of these technologies. By the time research has been performed, the technology used for a study has often become outdated and newer and more sophisticated imaging has become available. Methods We reviewed the literature on local and nodal staging of prostate cancer, as well as the role of magnetic resonance imaging (MRI), magnetic resonance spectroscopic imaging (MRSI), dynamic contrast-enhanced MRI, positron emission tomography (PET), endorectal power Doppler, lymphotropic MRI contrast agents, and future possibilities such as diffusion MRI. This review is not systematic, but rather focused on these imaging modalities. Results Advances in MRI, ultrasound, and lymphotropic contrast agents have improved our ability to differentiate between T2 and T3 prostate tumors. PET imaging has proven less successful at staging prostate cancer. A literature review suggests patients with moderate risk of extracapsular extension benefit most from endorectal MRI evaluation. Spectroscopy, dynamic imaging, and lymphotropic contrast agents are expected to continue to improve sensitivity and specificity of staging of prostate cancer. Power Doppler evaluation with endorectal ultrasound has proved useful for evaluation during endorectal biopsy for identifying hypervascular tumors for directed biopsy. Diffusion-weighted MRI remains untested clinically and represents a future direction for research. Conclusions Future studies using these new techniques are needed to demonstrate changes in outcomes in large patient populations.
Pathology of Germ Cell Tumors of the Testis
Authors: Sesterhenn Isabell A. , Davis Charles J. 
Published: August 2017

Background An increasing incidence of testis tumors has been noted over the second half of the 20th century. Congenital malformation of the male genitalia, prenatal risk factors, nonspecific and specific exposures in adulthood, and male infertility have all been associated with the etiology of germ cell tumors. Methods The histologic classification, pathology, and current concepts of testicular germ cell tumors are reviewed. Results Germ cell tumors occur at all ages. The tumors are identified as pure form (those of one histologic type) and mixed form (more than one histologic type). Over half of germ cell tumors consist of more than one cell type, requiring appropriate sampling for the correct diagnosis and correlation with the serum tumor markers. Burned-out germ cell tumors may occur in patients with metastatic disease with no gross evidence of a testicular tumor. Conclusions Appropriate management of testis tumors relies on accurate pathology and classification of these tumors.
Molecularly Targeted Therapies for Breast Cancer
Authors: Hobday Timothy J. , Perez Edith A. 
Published: August 2017

Background: The management of patients with localized and advanced breast cancer continues to evolve. Chemotherapy, endocrine therapy, and trastuzumab are effective therapies but leave considerable room for improvement. As the cellular aberrations inherent to cancer cells in general and breast cancer cells specifically are better understood, therapies to target specific cellular pathways continue to be developed with the goal of expanding available effective therapy through better patient selection. Methods: We conducted a computerized search of the medical literature as well as a manual search of selected meeting abstracts. Results: Several targeted therapies are in phase III clinical trials testing their promise in the treatment of breast cancer. Many other agents are completing phase I and II testing. An overview of the most promising agents in clinical development is discussed herein. Conclusions: Targeted therapy for breast cancer is a reality at this time, and several new agents hold promise for expanding and refining the pool of patients likely to further benefit from this approach in the near future.