Regarding complications following completion lymphadenectomy

Publication date: Available online 2 November 2017
Source:European Journal of Surgical Oncology
Author(s): Mark B. Faries, Alistair J. Cochran, John F. Thompson




http://ift.tt/2z9lDYn

A Potential Role for Green Tea as a Radiation Sensitizer for Prostate Cancer

Abstract

Prostate cancer (PCa) is the most common non-cutaneous cancer in the United States. There is currently a lack of safe and effective radiosensitizers that can enhance the effectiveness of radiation treatment (RT) for Pca. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis in DU145 Pca cells. RT-PCR/IHC were used to investigate the mechanisms. We found that the percentage of colonies, PCNA staining intensity, and the optical density value of DU145 cells were decreased (RT/GT vs. RT). TUNEL + cells and the relative caspase-3 activity were increased (RT/GT vs. RT). Compared to RT, the anti-proliferative effect of RT/GT correlated with increased expression of the anti-proliferative molecule p16. Compared to RT, the pro-apoptotic effect of RT/GT correlated with decreased expression of the anti-apoptotic molecule Bcl-2. GT enhances RT sensitivity of DU145 by inhibiting proliferation and promoting apoptosis.

http://ift.tt/2zb8L1o

Family Physicians’ Knowledge, Attitudes, and Practices Toward Colorectal Cancer Screening

Abstract

The purpose of this study was to assess family physicians' knowledge, attitudes, and practices toward colorectal cancer (CRC) screening. The population in this cross-sectional study consisted of 290 family physicians working in Samsun, Turkey, contacted between 15 June and 15 July 2015 and agreeing to participate. A questionnaire prepared by the authors on the basis of the relevant literature was applied at face-to-face interviews. The first part of the questionnaire inquired into sociodemographic information, while the second contained questions evaluating family physicians' knowledge, attitudes, and practices toward CRC screening. Physicians completed the questionnaire in approximately 10 min. 65.9 % of the family physicians in the study were men. Mean age of the participants was 43.40 ± 6.54 years, and mean number of years in service was 18.43 ± 6.42. The average number of patients seen by physicians on a daily basis was 51–99. CRC screening was performed by 83.1 % of physicians. The fecal occult blood test (FOBT) was recommended at the correct frequency by 30.7 % of physicians and colonoscopy by 11.7 %. A further 68.6 % of physicians followed no CRC guideline. Only 3.8 % of those reporting using a guideline were able to name it. The great majority of physicians in this study apply CRC screening. However, family physicians lack sufficient information concerning the ages at which screening tests should be started and concluded and how frequently they should be performed. They also do not attach sufficient importance to CRC guidelines. This results in excessive demand for screening tests.

http://ift.tt/2ioWOwY

Lessons Learned from Native C.I.R.C.L.E., a Culturally Specific Resource

Abstract

Cancer is now the second leading cause of death among American Indians and Alaska Natives (AIAN), and trends in cancer-related mortality over the past 2 decades show inferior control in AIAN compared to non-Hispanic Whites. The American Indian/Alaska Native Cancer Information Resource Center and Learning Exchange (Native C.I.R.C.L.E.) was developed in the year 2000 as part of a comprehensive network of partnerships to develop, maintain, and disseminate culturally appropriate cancer and other health information materials for AIAN educators and providers. Now, in its 15th year of existence, enough data has been accumulated by Native C.I.R.C.L.E. to analyze trends in the distribution of culturally relevant cancer information materials and compare access to both printed (hard copy) and online materials. The amount of culturally appropriate materials available since its creation has increased more than 10-fold. Print materials are now distributed throughout the world, and the number of materials requested from print and downloads combined are in the thousands on a monthly basis. Native C.I.R.C.L.E. is in the process of expanding its access and capabilities to target more of the lay AIAN public in order to address the digital divide.

http://ift.tt/2gY7Clm

Barriers to Completing Delayed Breast Reconstruction Following Mastectomy: a Critical Need for Patient and Clinician Education

Abstract

Rates of breast reconstruction following mastectomy vary widely, and little is known about why women who originally express an interest in breast reconstruction do not receive it. Improved documentation of clinical decision-making is one of the potential benefits of the electronic health record (EHR), and may serve as a tool to enhance patient-centered, clinical outcomes research. The goals of this study were to explore patterns in delayed reconstruction (DR), identify barriers to follow through, and to determine the adequacy of EHR documentation in providing information about decision-making for breast reconstruction. Retrospective EHR review of women undergoing mastectomy, 2008–2012, was conducted in an academic medical center in New England. Data included patient demographics, cancer stage, co-morbidity index, post-mastectomy reconstruction status, and documented decision-making regarding reconstruction. Of 367 women who had undergone a total mastectomy, 219 did not receive immediate reconstruction. Of these, 24.6 % expressed no interest in DR, 21.9 % expressed interest but were still pending the procedure, and 5.9 % had completed DR. Of decision-making regarding breast reconstruction, 47.5 % lacked documentation. Median follow-up was 34 months. Reasons for not following through with DR included poor timing (25 %), indecision (17 %), desired method of reconstruction not available at treating facility (10 %), persistent obesity (8.3 %), continued smoking (4 %), and reason not specified (35 %). Many women do not receive breast reconstruction despite expressing an initial interest in the procedure. Reasons were multi-factorial and the extent of documentation was inconsistent. Further exploration of potential barriers to breast reconstruction as well as opportunities to enhance shared decision-making may serve to improve patient experience and satisfaction following mastectomy.

http://ift.tt/2ipLHnP

Reflections on Writing an Engaging Patient Blog

Abstract

Blogs can be a novel way to engage patients in a virtual manner. This reflections article provides highlights on how to get started writing a patient blog as well as practical tips to make your patient blog successful. Empowering patients to learn and share through a blog may bring a new level of insight to your education practice.

http://ift.tt/2gY7x12

Cultural Competency Training to Increase Minority Enrollment into Radiation Therapy Clinical Trials—an NRG Oncology RTOG Study

Abstract

Despite initiatives to increase the enrollment of racial and ethnic minorities into cancer clinical trials in the National Cancer Institute National Cancer Clinical Trials Network (NCCTN), participation by Latino and African American populations remain low. The primary aims of this pilot study are (1) to develop a Cultural Competency and Recruitment Training Program (CCRTP) for physician investigators and clinical research associates (CRAs), (2) to determine if the CCRTP increases cultural competency scores among physician investigators and CRAs, and (3) to determine the impact of the CCRTP on minority patient recruitment into NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials. Sixty-seven CRAs and physicians participated in an in-person or online 4-h CRRTP training. Five knowledge and attitude items showed significant improvements from pre- to post-training. A comparison between enrolling sites that did and did not participate in the CCRTP demonstrated a pre to 1-year post-incremental increase in minority accrual to clinical trials of 1.2 % among participating sites. While not statistically significant, this increase translated into an additional 300 minority patients accrued to NCCTN clinical trials in the year following the training from those sites who participated in the training.

http://ift.tt/2ioWIW8

The Content and Quality of Health Information on the Internet for Patients and Families on Adult Kidney Cancer

Abstract

The Internet is one of the major sources for health information for patients and their families, particularly when patients face serious life-threatening conditions such as kidney cancer in adults. In this study, we evaluate the content and quality of health information on adult kidney cancer using several validated instruments. We accessed the three most popular search engines (Google, Yahoo, Bing), using two terms: "kidney cancer" and "renal cell carcinoma," and reviewed the top 30 hits. After exclusion of duplicated websites, websites targeting health care professionals, and unrelated websites, 35 websites were included. Content was assessed using a 22-item checklist adapted from the American Cancer Society. We assessed website quality using the DISCERN questionnaire, HONcode and JAMA benchmark criteria, readability using three readability scores, and ALEXA for global traffic ranking systems. The average website had 16 of 22 content items while 6 websites fulfilled all 22 items. Among all websites, the average DISCERN quality score was 42 out of 80, 15 (42.8 %) of websites had HONcode certification, and only 3 (8.5 %) fulfilled all JAMA benchmark criteria. The average website readability was at the ninth grade reading level. The content and quality of health-related information on the Internet for adult kidney cancer are variable in comprehensiveness and quality. Many websites are difficult to read without a high school education. A standardized approach to presenting cancer information on the Internet for patients and families may be warranted.

http://ift.tt/2gYie3Z

The Perceptions and Expectations of Older Women in the Establishment of the Senior Women’s Breast Cancer Clinic (SWBCC): a Needs Assessment Study

Abstract

This study explored older women's perceptions and expectations of the prospective Senior Women's Breast Cancer Clinic (SWBCC) at Sunnybrook Odette Cancer Centre (SOCC) in Toronto, Ontario, Canada. In our previous studies, older breast cancer patients had expressed a greater need for informational, decisional, and post-treatment support. This study also assessed women's perspectives on the involvement of geriatricians and incorporation of geriatric assessment in their cancer care. Twelve breast cancer patients aged 68 years or older who were treated at the SOCC participated in the study. We recorded and transcribed 11 interviews and analyzed them using qualitative thematic analysis methods to identify major themes; one interview was excluded due to recording defect. Eight major themes were identified: transportation issues, service, communication between patient and healthcare professionals, communication between healthcare professionals, support during treatment, support after treatment, informational resources, and patient suggestions. Important issues were raised by participants, such as difficulties in arranging transportation to the clinic, barriers in accessing family physician service, and communication breakdown that result in treatment delay and unaddressed complications. In conclusion, there were important gaps in the cancer care of older women with breast cancer that could be detected earlier and better addressed in the new multidisciplinary SWBCC. The participating women were highly supportive of the initiative and made several suggestions on how the clinic could better accommodate their specific needs during and after breast cancer treatment.

http://ift.tt/2ipLBwt

Family Physicians’ Knowledge, Attitudes, and Practices Toward Colorectal Cancer Screening

Abstract

The purpose of this study was to assess family physicians' knowledge, attitudes, and practices toward colorectal cancer (CRC) screening. The population in this cross-sectional study consisted of 290 family physicians working in Samsun, Turkey, contacted between 15 June and 15 July 2015 and agreeing to participate. A questionnaire prepared by the authors on the basis of the relevant literature was applied at face-to-face interviews. The first part of the questionnaire inquired into sociodemographic information, while the second contained questions evaluating family physicians' knowledge, attitudes, and practices toward CRC screening. Physicians completed the questionnaire in approximately 10 min. 65.9 % of the family physicians in the study were men. Mean age of the participants was 43.40 ± 6.54 years, and mean number of years in service was 18.43 ± 6.42. The average number of patients seen by physicians on a daily basis was 51–99. CRC screening was performed by 83.1 % of physicians. The fecal occult blood test (FOBT) was recommended at the correct frequency by 30.7 % of physicians and colonoscopy by 11.7 %. A further 68.6 % of physicians followed no CRC guideline. Only 3.8 % of those reporting using a guideline were able to name it. The great majority of physicians in this study apply CRC screening. However, family physicians lack sufficient information concerning the ages at which screening tests should be started and concluded and how frequently they should be performed. They also do not attach sufficient importance to CRC guidelines. This results in excessive demand for screening tests.

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via IFTTT

Lessons Learned from Native C.I.R.C.L.E., a Culturally Specific Resource

Abstract

Cancer is now the second leading cause of death among American Indians and Alaska Natives (AIAN), and trends in cancer-related mortality over the past 2 decades show inferior control in AIAN compared to non-Hispanic Whites. The American Indian/Alaska Native Cancer Information Resource Center and Learning Exchange (Native C.I.R.C.L.E.) was developed in the year 2000 as part of a comprehensive network of partnerships to develop, maintain, and disseminate culturally appropriate cancer and other health information materials for AIAN educators and providers. Now, in its 15th year of existence, enough data has been accumulated by Native C.I.R.C.L.E. to analyze trends in the distribution of culturally relevant cancer information materials and compare access to both printed (hard copy) and online materials. The amount of culturally appropriate materials available since its creation has increased more than 10-fold. Print materials are now distributed throughout the world, and the number of materials requested from print and downloads combined are in the thousands on a monthly basis. Native C.I.R.C.L.E. is in the process of expanding its access and capabilities to target more of the lay AIAN public in order to address the digital divide.

from Cancer via ola Kala on Inoreader http://ift.tt/2gY7Clm
via IFTTT

Barriers to Completing Delayed Breast Reconstruction Following Mastectomy: a Critical Need for Patient and Clinician Education

Abstract

Rates of breast reconstruction following mastectomy vary widely, and little is known about why women who originally express an interest in breast reconstruction do not receive it. Improved documentation of clinical decision-making is one of the potential benefits of the electronic health record (EHR), and may serve as a tool to enhance patient-centered, clinical outcomes research. The goals of this study were to explore patterns in delayed reconstruction (DR), identify barriers to follow through, and to determine the adequacy of EHR documentation in providing information about decision-making for breast reconstruction. Retrospective EHR review of women undergoing mastectomy, 2008–2012, was conducted in an academic medical center in New England. Data included patient demographics, cancer stage, co-morbidity index, post-mastectomy reconstruction status, and documented decision-making regarding reconstruction. Of 367 women who had undergone a total mastectomy, 219 did not receive immediate reconstruction. Of these, 24.6 % expressed no interest in DR, 21.9 % expressed interest but were still pending the procedure, and 5.9 % had completed DR. Of decision-making regarding breast reconstruction, 47.5 % lacked documentation. Median follow-up was 34 months. Reasons for not following through with DR included poor timing (25 %), indecision (17 %), desired method of reconstruction not available at treating facility (10 %), persistent obesity (8.3 %), continued smoking (4 %), and reason not specified (35 %). Many women do not receive breast reconstruction despite expressing an initial interest in the procedure. Reasons were multi-factorial and the extent of documentation was inconsistent. Further exploration of potential barriers to breast reconstruction as well as opportunities to enhance shared decision-making may serve to improve patient experience and satisfaction following mastectomy.

from Cancer via ola Kala on Inoreader http://ift.tt/2ipLHnP
via IFTTT

Reflections on Writing an Engaging Patient Blog

Abstract

Blogs can be a novel way to engage patients in a virtual manner. This reflections article provides highlights on how to get started writing a patient blog as well as practical tips to make your patient blog successful. Empowering patients to learn and share through a blog may bring a new level of insight to your education practice.

from Cancer via ola Kala on Inoreader http://ift.tt/2gY7x12
via IFTTT

Cultural Competency Training to Increase Minority Enrollment into Radiation Therapy Clinical Trials—an NRG Oncology RTOG Study

Abstract

Despite initiatives to increase the enrollment of racial and ethnic minorities into cancer clinical trials in the National Cancer Institute National Cancer Clinical Trials Network (NCCTN), participation by Latino and African American populations remain low. The primary aims of this pilot study are (1) to develop a Cultural Competency and Recruitment Training Program (CCRTP) for physician investigators and clinical research associates (CRAs), (2) to determine if the CCRTP increases cultural competency scores among physician investigators and CRAs, and (3) to determine the impact of the CCRTP on minority patient recruitment into NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials. Sixty-seven CRAs and physicians participated in an in-person or online 4-h CRRTP training. Five knowledge and attitude items showed significant improvements from pre- to post-training. A comparison between enrolling sites that did and did not participate in the CCRTP demonstrated a pre to 1-year post-incremental increase in minority accrual to clinical trials of 1.2 % among participating sites. While not statistically significant, this increase translated into an additional 300 minority patients accrued to NCCTN clinical trials in the year following the training from those sites who participated in the training.

from Cancer via ola Kala on Inoreader http://ift.tt/2ioWIW8
via IFTTT

The Content and Quality of Health Information on the Internet for Patients and Families on Adult Kidney Cancer

Abstract

The Internet is one of the major sources for health information for patients and their families, particularly when patients face serious life-threatening conditions such as kidney cancer in adults. In this study, we evaluate the content and quality of health information on adult kidney cancer using several validated instruments. We accessed the three most popular search engines (Google, Yahoo, Bing), using two terms: "kidney cancer" and "renal cell carcinoma," and reviewed the top 30 hits. After exclusion of duplicated websites, websites targeting health care professionals, and unrelated websites, 35 websites were included. Content was assessed using a 22-item checklist adapted from the American Cancer Society. We assessed website quality using the DISCERN questionnaire, HONcode and JAMA benchmark criteria, readability using three readability scores, and ALEXA for global traffic ranking systems. The average website had 16 of 22 content items while 6 websites fulfilled all 22 items. Among all websites, the average DISCERN quality score was 42 out of 80, 15 (42.8 %) of websites had HONcode certification, and only 3 (8.5 %) fulfilled all JAMA benchmark criteria. The average website readability was at the ninth grade reading level. The content and quality of health-related information on the Internet for adult kidney cancer are variable in comprehensiveness and quality. Many websites are difficult to read without a high school education. A standardized approach to presenting cancer information on the Internet for patients and families may be warranted.

from Cancer via ola Kala on Inoreader http://ift.tt/2gYie3Z
via IFTTT

The Perceptions and Expectations of Older Women in the Establishment of the Senior Women’s Breast Cancer Clinic (SWBCC): a Needs Assessment Study

Abstract

This study explored older women's perceptions and expectations of the prospective Senior Women's Breast Cancer Clinic (SWBCC) at Sunnybrook Odette Cancer Centre (SOCC) in Toronto, Ontario, Canada. In our previous studies, older breast cancer patients had expressed a greater need for informational, decisional, and post-treatment support. This study also assessed women's perspectives on the involvement of geriatricians and incorporation of geriatric assessment in their cancer care. Twelve breast cancer patients aged 68 years or older who were treated at the SOCC participated in the study. We recorded and transcribed 11 interviews and analyzed them using qualitative thematic analysis methods to identify major themes; one interview was excluded due to recording defect. Eight major themes were identified: transportation issues, service, communication between patient and healthcare professionals, communication between healthcare professionals, support during treatment, support after treatment, informational resources, and patient suggestions. Important issues were raised by participants, such as difficulties in arranging transportation to the clinic, barriers in accessing family physician service, and communication breakdown that result in treatment delay and unaddressed complications. In conclusion, there were important gaps in the cancer care of older women with breast cancer that could be detected earlier and better addressed in the new multidisciplinary SWBCC. The participating women were highly supportive of the initiative and made several suggestions on how the clinic could better accommodate their specific needs during and after breast cancer treatment.

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Pembrolizumab for treatment of advanced gastric and gastroesophageal junction adenocarcinoma

Future Oncology, Ahead of Print.


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Pembrolizumab for treatment of advanced gastric and gastroesophageal junction adenocarcinoma

Future Oncology, Ahead of Print.


http://ift.tt/2h8H3xR

Pembrolizumab for treatment of advanced gastric and gastroesophageal junction adenocarcinoma

Future Oncology, Ahead of Print.


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via IFTTT

Data Science in Radiology: A Path Forward

Artificial intelligence (AI), especially deep learning, has the potential to fundamentally alter clinical radiology. AI algorithms, which excel in quantifying complex patterns in data, have shown remarkable progress in applications ranging from self-driving cars to speech recognition. The AI application within radiology, known as radiomics, can provide detailed quantifications of the radiographic characteristics of underlying tissues. This information can be used throughout the clinical care path to improve diagnosis and treatment planning, as well as assess treatment response. This tremendous potential for clinical translation has led to a vast increase in the number of research studies being conducted in the field, a number that is expected to rise sharply in the future. Many studies have reported robust and meaningful findings; however, a growing number also suffer from flawed experimental or analytical designs. Such errors could not only can result in invalid discoveries, but also may lead others to perpetuate similar flaws in their own work. This perspective article aims to increase awareness of the issue, identify potential reasons why this is happening, and provide a path forward.

http://ift.tt/2iZogp1

Data Science in Radiology: A Path Forward

Artificial intelligence (AI), especially deep learning, has the potential to fundamentally alter clinical radiology. AI algorithms, which excel in quantifying complex patterns in data, have shown remarkable progress in applications ranging from self-driving cars to speech recognition. The AI application within radiology, known as radiomics, can provide detailed quantifications of the radiographic characteristics of underlying tissues. This information can be used throughout the clinical care path to improve diagnosis and treatment planning, as well as assess treatment response. This tremendous potential for clinical translation has led to a vast increase in the number of research studies being conducted in the field, a number that is expected to rise sharply in the future. Many studies have reported robust and meaningful findings; however, a growing number also suffer from flawed experimental or analytical designs. Such errors could not only can result in invalid discoveries, but also may lead others to perpetuate similar flaws in their own work. This perspective article aims to increase awareness of the issue, identify potential reasons why this is happening, and provide a path forward.

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Copyright

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4





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Contributors

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4





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Contents

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4





http://ift.tt/2zdElh3

Forthcoming Issues

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4





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Anesthesia Outside of the Operating Room: The Wild West or the New Frontier?

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Lee A. Fleisher




http://ift.tt/2ze45di

Anesthesia Outside the Operating Room

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Mark S. Weiss, Wendy L. Gross




http://ift.tt/2zstLUl

Anesthesia Outside the Operating Room

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Mark S. Weiss, Wendy L. Gross




http://ift.tt/2zeoiPY

Demands of Integrated Care Delivery in Interventional Medicine and Anesthesiology

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Wendy L. Gross, Lebron Cooper, Steven Boggs

Teaser

Evolving financial and medical constraints fueled by the increasing repertoire of nonoperating room cases and widening scope of patient comorbidities are discussed. The need to integrate finances and care approaches is detailed, and strategic suggestions for broader collaborative practice are suggested.


http://ift.tt/2ztuvIT

Building and Maintaining Organizational Infrastructure to Attain Clinical Excellence

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Kelly Lebak, Jason Lane, Richard Taus, Hansol Kim, Michael S. Stecker, Michael Hall, Meghan B. Lane-Fall, Mark S. Weiss

Teaser

Active maintenance of highly functional teams is critical to ensuring safe, efficient patient care in the non–operating room anesthesia (NORA) suite. In addition to developing collaborative relationships and patient care protocols, individual and team training is needed. For anesthesiologists, this training must begin during residency. The training should be supplemented with continuing education in this field for providers who find themselves working in the NORA space. As NORA continues to grow, robust NORA-specific quality assurance and improvement programs will empower anesthesiologists with the tools they need to best care for these patients.


http://ift.tt/2zeoazY

Safety of Non–Operating Room Anesthesia

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Zachary G. Woodward, Richard D. Urman, Karen B. Domino

Teaser

Malpractice claims for non–operating room anesthesia care (NORA) had a higher proportion of claims for death than claims in operating rooms (ORs). NORA claims most frequently involved monitored anesthesia care. Inadequate oxygenation/ventilation was responsible for one-third of NORA claims, often judged probably preventable by better monitoring. Fewer malpractice claims for NORA occurred than for OR anesthesia as assessed by the relative numbers of in NORA versus OR procedures. The proportion of claims in cardiology and radiology NORA locations were increased compared with estimates of cases in these locations. Although NORA is safe, adherence to safe clinical practice is important.


http://ift.tt/2ztupB1

Implementation and Use of Anesthesia Information Management Systems for Non–operating Room Locations

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Jason T. Bouhenguel, David A. Preiss, Richard D. Urman

Teaser

Non–operating room anesthesia (NORA) encounters comprise a significant fraction of contemporary anesthesia practice. With the implemention of an aneshtesia information management system (AIMS), anesthesia practitioners can better streamline preoperative assessment, intraoperative automated documentation, real-time decision support, and remote surveillance. Despite the large personal and financial commitments involved in adoption and implementation of AIMS and other electronic health records in these settings, the benefits to safety, efficacy, and efficiency are far too great to be ignored. Continued future innovation of AIMS technology only promises to further improve on our NORA experience and improve care quality and safety.


http://ift.tt/2zdE1il

Monitoring for Nonoperating Room Anesthesia

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Stylianos Voulgarelis, John P. Scott

Teaser

Procedures requiring nonoperating room anesthesia (NORA) continue to increase in quantity and complexity. The roles of anesthesiologists as members of care teams in nonoperating room locations continue to evolve. The safe provision of NORA requires strict adherence to standardized monitoring guidelines including pulse oximetry, capnography, electrocardiogram, and noninvasive blood pressure ampliflier. Body temperature should also be measured in appropriate scenarios. High-risk anesthetics require advanced preparation and monitoring.


http://ift.tt/2ztum8j

Use of Anesthesiology Services in Radiology

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Hansol Kim, Jason Lane, Rolf Schlichter, Michael S. Stecker, Richard Taus

Teaser

In the setting of technological advancements in imaging and intervention with concomitant rise in the use of non–operating room anesthesia (NORA) care, it has become even more critical for anesthesiologists to be aware of the needs and limitations of interventional procedures performed outside of the operating room. This article addresses the use of NORA services from the interventional radiologist's point of view and provides specific examples of preprocedural, intraprocedural, and postprocedural care patients may need for optimal outcome.


http://ift.tt/2zfYrr9

An Anesthesiologist’s View of Tumor Ablation in the Radiology Suite

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Annie Amin, Jason Lane, Thomas Cutter

Teaser

The advent of radiology image–guided tumor ablation procedures has opened up a new era in minimally invasive procedures. Using CT, MRI, ultrasound, and other modalities, radiologists and surgeons can now ablate a tumor through percutaneous entry sites. What traditionally was done in an operating room via large open incisions, with multiple days in the hospital recovering, is now becoming an outpatient procedure via these new techniques. Anesthesiologists play a critical role in optimizing outcome in these patients. Knowledge by anesthesiologists of procedural goals, technology used, and inherit safety concerns of anesthetizing patients in the radiology suite are all critical to patients and proceduralists.


http://ift.tt/2ztue8P

A Radiologist’s View of Tumor Ablation in the Radiology Suite

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Sharath K. Bhagavatula, Jason Lane, Paul Shyn

Teaser

Image-guided percutaneous, minimally invasive ablation techniques offer a wide variety of new modalities to treat tumors in some of the most medically complicated patients coming to our hospitals. The use of computed tomography, PET, ultrasound imaging, and MRI to guide radiofrequency ablation, microwave ablation, and cryoablation techniques now makes it possible to treat patients on a short stay or outpatient basis with very good immediate outcomes. This rapid expansion of new tumor ablation techniques often presents challenges for the non–operating room anesthesia team. Collaboration and communication between the radiologist and anesthesiologist are key to safety and excellent patient outcomes.


http://ift.tt/2zdVbMW

Catheterization Laboratory

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Paul N. Fiorilli, Saif Anwaruddin, Elizabeth Zhou, Ronak Shah

Teaser

The cardiac catheterization laboratory is advancing medicine by performing procedures on patients who would usually require sternotomy and cardiopulmonary bypass. These procedures are done percutaneously, allowing them to be performed on patients considered inoperable. Patients have compromised cardiovascular function or advanced age. An anesthesiologist is essential for these procedures in case of hemodynamic compromise. Interventionalists are becoming more familiar with transcatheter aortic valve replacement and the device has become smaller, both contributing to less complications. Left atrial occlusion and the endovascular edge-to-edge mitral valve repair devices were approved. Although these devices require general anesthesia, an invasive surgery and cardiopulmonary bypass machine are not necessary for deployment.


http://ift.tt/2zstkJH

Anesthesia in the Electrophysiology Laboratory

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Jeff E. Mandel, William G. Stevenson, David S. Frankel

Teaser

The electrophysiology suite is a foreign location to many anesthesiologists. The initial experience was with shorter procedures under conscious sedation, and the value of greater tailoring of the sedation/anesthesia by anesthesiologists was not perceived until practice patterns had already been established. Although better control of ventilation with general anesthesia may be expected, suppression of arrhythmias, blunting of the hemodynamic adaptation to induced arrhythmias, and interference by muscle relaxants with identification of the phrenic nerve may be seen. We review a range of electrophysiology procedures and discuss anesthetic approaches that balance patient safety and favorable outcomes.


http://ift.tt/2zdV7Nc

Cardioversions and Transthoracic Echocardiography

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Ronak Shah, Elizabeth Zhou

Teaser

Patients with atrial fibrillation and flutter routinely require transesophageal echocardiography with cardioversion. It is not uncommon to encounter patients with reduced ejection fractions, coronary artery disease, prior cardiac surgery, or obstructive sleep apnea. The anesthesiologist must carefully evaluate the patient and any available laboratory and study findings to assess for potential complications after anesthesia. Appropriate anesthetics must be chosen based on the preoperative evaluation. Additionally, because most of these cases are done without a secured airway, emergency medications and airway equipment must be readily available.


http://ift.tt/2ztu15x

Anesthesia for Routine and Advanced Upper Gastrointestinal Endoscopic Procedures

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): Christopher D. Sharp, Ezekiel Tayler, Gregory G. Ginsberg

Teaser

This article aims to detail the breadth and depth of advanced upper gastrointestinal endoscopic procedures. It will focus on sedation and airway management concerns pertaining to this emerged and emerging class of minimally invasive interventions. The article will also cover endoscopic hemostasis, endoscopic resection, stenting and Barrett eradication therapy plus endoscopic ultrasound. It additionally will address the nuances of endoscopic retrograde cholangiopancreatography and new natural orifice transluminal endoscopic surgery procedures including endoscopic cystgastrostomy and the per-oral endoscopic myotomy procedure.


http://ift.tt/2zdV4B0

Anesthesia for Colonoscopy and Lower Endoscopic Procedures

Publication date: December 2017
Source:Anesthesiology Clinics, Volume 35, Issue 4
Author(s): John Michael Trummel, Vinay Chandrasekhara, Michael L. Kochman

Teaser

Demand for anesthesiologist-assisted sedation is expanding for gastrointestinal lower endoscopic procedures and may add to the cost of these procedures. Most lower endoscopy can be accomplished with either no, moderate, or deep sedation; general anesthesia and active airway management are rarely needed. Propofol-based sedation has advantages in terms of satisfaction and recovery over other modalities, but moderate sedation using benzodiazepines and opiates work well for low-risk patients and procedures. No sedation for routine colonoscopy works well for selected patients and eliminates sedation-related risks. There is no difference in outcome measures based on sedation received.


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IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms

Abstract

Background

To date, the estimated radiation-absorbed dose to organs and tissues in patients undergoing diagnostic examinations in nuclear medicine is derived via calculations based on models of the human body and the biokinetic behaviour of the radiopharmaceutical. An internal dosimetry computer program, IDAC-Dose2.1, was developed based on the International Commission on Radiological Protection (ICRP)-specific absorbed fractions and computational framework of internal dose assessment given for reference adults in ICRP Publication 133. The program uses the radionuclide decay database of ICRP Publication 107 and considers 83 different source regions irradiating 47 target tissues, defining the effective dose as presented in ICRP Publications 60 and 103. The computer program was validated against another ICRP dosimetry program, Dose and Risk Calculation (DCAL), that employs the same computational framework in evaluation of occupational and environmental intakes of radionuclides. IDAC-Dose2.1 has a sub-module for absorbed dose calculations in spherical structures of different volumes and composition; this sub-module is intended for absorbed dose estimates in radiopharmaceutical therapy. For nine specific alpha emitters, the absorbed dose contribution from their decay products is also included in the committed absorbed dose calculations.

Results

The absorbed doses and effective dose of ¹³¹I-iodide determined by IDAC-Dose2.1 were validated against the dosimetry program DCAL, showing identical results. IDAC-Dose2.1 was used to calculate absorbed doses for intravenously administered ¹⁸F-FDG and orally administered ^99mTc-pertechnetate and ¹³¹I-iodide, three frequently used radiopharmaceuticals. Using the tissue weighting factors from ICRP Publication 103, the effective dose per administered activity was estimated to be 0.016 mSv/MBq for ¹⁸F-FDG, 0.014 mSv/MBq for ^99mTc-pertechnetate, and 16 mSv/MBq for ¹³¹I-iodide.

Conclusions

The internal dosimetry program IDAC-Dose2.1 was developed and applied to three radiopharmaceuticals for validation against DCAL and to generate improved absorbed dose estimations for diagnostic nuclear medicine using specific absorbed fraction values of the ICRP computational voxel phantoms. The sub-module for absorbed dose calculations in spherical structures 1 mm to 9 cm in diameter and different tissue composition was included to broaden the clinical usefulness of the program. The IDAC-Dose2.1 program is free software for research and available for download at http://ift.tt/2iqKoVz.

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IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms

Abstract

Background

To date, the estimated radiation-absorbed dose to organs and tissues in patients undergoing diagnostic examinations in nuclear medicine is derived via calculations based on models of the human body and the biokinetic behaviour of the radiopharmaceutical. An internal dosimetry computer program, IDAC-Dose2.1, was developed based on the International Commission on Radiological Protection (ICRP)-specific absorbed fractions and computational framework of internal dose assessment given for reference adults in ICRP Publication 133. The program uses the radionuclide decay database of ICRP Publication 107 and considers 83 different source regions irradiating 47 target tissues, defining the effective dose as presented in ICRP Publications 60 and 103. The computer program was validated against another ICRP dosimetry program, Dose and Risk Calculation (DCAL), that employs the same computational framework in evaluation of occupational and environmental intakes of radionuclides. IDAC-Dose2.1 has a sub-module for absorbed dose calculations in spherical structures of different volumes and composition; this sub-module is intended for absorbed dose estimates in radiopharmaceutical therapy. For nine specific alpha emitters, the absorbed dose contribution from their decay products is also included in the committed absorbed dose calculations.

Results

The absorbed doses and effective dose of ¹³¹I-iodide determined by IDAC-Dose2.1 were validated against the dosimetry program DCAL, showing identical results. IDAC-Dose2.1 was used to calculate absorbed doses for intravenously administered ¹⁸F-FDG and orally administered ^99mTc-pertechnetate and ¹³¹I-iodide, three frequently used radiopharmaceuticals. Using the tissue weighting factors from ICRP Publication 103, the effective dose per administered activity was estimated to be 0.016 mSv/MBq for ¹⁸F-FDG, 0.014 mSv/MBq for ^99mTc-pertechnetate, and 16 mSv/MBq for ¹³¹I-iodide.

Conclusions

The internal dosimetry program IDAC-Dose2.1 was developed and applied to three radiopharmaceuticals for validation against DCAL and to generate improved absorbed dose estimations for diagnostic nuclear medicine using specific absorbed fraction values of the ICRP computational voxel phantoms. The sub-module for absorbed dose calculations in spherical structures 1 mm to 9 cm in diameter and different tissue composition was included to broaden the clinical usefulness of the program. The IDAC-Dose2.1 program is free software for research and available for download at http://ift.tt/2iqKoVz.

http://ift.tt/2h0bCSN

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model, Published online: 02 November 2017; doi:10.1038/bjc.2017.375

http://ift.tt/2iWrycX

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma, Published online: 02 November 2017; doi:10.1038/bjc.2017.373

http://ift.tt/2iXFzXI

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030, Published online: 02 November 2017; doi:10.1038/bjc.2017.341

http://ift.tt/2iZhK1x

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model, Published online: 02 November 2017; doi:10.1038/bjc.2017.375

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Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma, Published online: 02 November 2017; doi:10.1038/bjc.2017.373

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Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030, Published online: 02 November 2017; doi:10.1038/bjc.2017.341

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Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

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Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

http://ift.tt/2lKbw6H

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

http://ift.tt/2yrzGsy

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

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Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

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Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

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The Use of Regional or Neuraxial Anesthesia for Below-Knee Amputations May Reduce the Need for Perioperative Blood Transfusions.

Background and Objectives: Amputations of the lower extremity remain a common procedure in a high-risk population. Perioperative morbidity and mortality reach as high as 14.1% in below-knee amputations. We aimed to determine whether regional, or neuraxial, anesthesia, when compared with general anesthesia (GA), would be associated with reduced perioperative morbidity and mortality. Methods: We queried the American College of Surgeons National Surgical Quality Improvement Program data set. The study population was divided into 2 groups: patients undergoing regional anesthesia (RA) and those undergoing GA. The primary end point for our study was 30-day mortality. The secondary end points were return to the operating room, surgical site infections, pulmonary complications, acute kidney injury, urinary tract infection, cardiac arrest, myocardial infarction, perioperative transfusions, thromboembolisms, sepsis, composite measure of postoperative complications, and days from operation to discharge. Results: Twelve thousand seven hundred twenty-three patients were identified. Older patients, white patients, patients with a higher body mass index, patients without dyspnea, patients with independent functional status, smokers, patients with sepsis, and patients with bleeding disorders were associated with receiving GA. Hispanic patients, patients with chronic obstructive pulmonary disease, and patients with congestive heart failure were associated with receiving RA. Our study did not reveal a 30-day mortality difference between RA and GA. Regional anesthesia was associated with a significantly decreased need for perioperative blood transfusions (11.8% vs 16.5%, P

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Challenging Conventions to Make a Difference in Patient Care: The 2017 Gaston Labat Award Lecture.

No abstract available

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Correlates of post-traumatic growth following childhood and adolescent cancer: a systematic review and meta-analysis

Abstract

Objective

Post-traumatic growth is defined as positive change resulting from the struggle with highly challenging life circumstances or trauma [1]. A growing number of children and adolescents are experiencing and surviving cancer. This review aims to identify the demographic, medical, and psychosocial correlates of perceived post-traumatic growth in individuals of any age who were affected by paediatric cancer. Findings will highlight protective factors that may facilitate post-traumatic growth, allowing for directed social support, intervention, and follow-up care.

Methods

A systematic search based on the key concepts "post-traumatic growth", "neoplasms", and "paediatric" retrieved 905 records from online databases; Embase, Ovid MedLINE, PILOTS: Published International Literature on Traumatic Stress, PsycINFO, and Web of Science. Eligible studies were appraised as excellent quality with a high level of inter-rater reliability. The results of eighteen studies were synthesised.

Results

After the removal of outliers, post-traumatic growth shared small, negative associations with time since diagnosis (r = -.14) and time since treatment completion (r = -.19), and small, positive associations with age at diagnosis (r = .20), age at survey (r = .17), post-traumatic stress symptoms (r = .11), and social support (r = .25). Post-traumatic growth was positively and moderately associated with optimism (r = .31).

Conclusions

Several findings were consistent with a comparable meta-analysis in adult oncology populations. Targeted social support, clinical intervention, and education may facilitate post-traumatic growth. Longitudinal research in individuals affected by childhood and adolescent cancer would allow an examination of the effects of predictive variables on post-traumatic growth over time.

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Correlates of post-traumatic growth following childhood and adolescent cancer: a systematic review and meta-analysis

Abstract

Objective

Post-traumatic growth is defined as positive change resulting from the struggle with highly challenging life circumstances or trauma [1]. A growing number of children and adolescents are experiencing and surviving cancer. This review aims to identify the demographic, medical, and psychosocial correlates of perceived post-traumatic growth in individuals of any age who were affected by paediatric cancer. Findings will highlight protective factors that may facilitate post-traumatic growth, allowing for directed social support, intervention, and follow-up care.

Methods

A systematic search based on the key concepts "post-traumatic growth", "neoplasms", and "paediatric" retrieved 905 records from online databases; Embase, Ovid MedLINE, PILOTS: Published International Literature on Traumatic Stress, PsycINFO, and Web of Science. Eligible studies were appraised as excellent quality with a high level of inter-rater reliability. The results of eighteen studies were synthesised.

Results

After the removal of outliers, post-traumatic growth shared small, negative associations with time since diagnosis (r = -.14) and time since treatment completion (r = -.19), and small, positive associations with age at diagnosis (r = .20), age at survey (r = .17), post-traumatic stress symptoms (r = .11), and social support (r = .25). Post-traumatic growth was positively and moderately associated with optimism (r = .31).

Conclusions

Several findings were consistent with a comparable meta-analysis in adult oncology populations. Targeted social support, clinical intervention, and education may facilitate post-traumatic growth. Longitudinal research in individuals affected by childhood and adolescent cancer would allow an examination of the effects of predictive variables on post-traumatic growth over time.

http://ift.tt/2ypgr2Y

Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling

Clinically, breast cancer is generally classified into estrogen receptor-positive (ER+) or estrogen receptor-negative (ER−) subtypes. The phytoestrogen calycosin has been shown to inhibit the proliferation of ...

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Circular RNAs: emerging cancer biomarkers and targets

CircRNAs are a class of RNA molecules that structurally form closed loops. CircRNAs are abundant in eukaryotic transcripts and show certain levels of tissue and cell specificity. CircRNAs have been suggested t...

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The anti-tumor effect of RANKL inhibition in malignant solid tumors – a systematic review

Publication date: Available online 1 November 2017
Source:Cancer Treatment Reviews
Author(s): AF. de Groot, NM. Appelman-Dijkstra, SH. van der Burg, JR. Kroep
At present, accumulating evidence suggests that inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) does not only induce an increase in bone mass and strength, but also has anti-tumor effects. Denosumab, an antibody targeting RANKL, is used to treat osteoporosis and to prevent skeletal related events (SREs) in patients with bone metastases originating from solid tumors. However, expression of RANKL and its receptor activator of nuclear factor kappa-B (RANK) is not solely restricted to cells involved in homeostasis of the bone and RANKL-RANK signalling appears to play a substantial role in many other processes in the body like mammary physiology, mammary tumorigenesis and the immune system. In pre-clinical models, RANKL inhibition has been shown to reduce skeletal tumor burden and distant metastases as well as to decrease mammary carcinogenesis. Clinically, RANKL inhibition improves bone-metastasis free survival in patients with prostate cancer and disease-free survival in patients with breast cancer. In addition, RANKL treatment may form a preventative strategy in patients at high risk for malignancies of the breast. Current clinical studies are evaluating the effect of denosumab on survival, the immune system and other biomarkers into a greater extent. To that purpose, a systematic review of the literature was performed and a narrative review synthesized, describing the present pre-clinical and clinical evidence of an anti-tumor effect of RANKL inhibition and the potential role of the immune system as one of the underlying mechanisms.



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The effects of lapatinib on CYP3A metabolism of midazolam in patients with advanced cancer

Abstract

Purpose

The potential inhibition of CYP3A4 by lapatinib was studied using midazolam as a probe substrate in patients with cancer.

Methods

This was a partially randomized, 4-period, 4-sequence, 4-treatment, cross-over study in 24 patients with advanced cancer. Single 1-mg IV and 3-mg oral doses of midazolam were given 2 days apart, in a partially random order, on study days 1, 3, 9, and 11. Lapatinib 1500-mg was administered orally once daily on study days 4 through 11. Midazolam plasma concentrations were measured up to 24-h post dosing, and lapatinib plasma concentrations measured prior to each midazolam dose.

Results

Lapatinib increased the geometric mean (95% CIs) midazolam AUC_(o−∞) by 45% (31–60%) after the oral dose and by 14% (0–29%) after the IV dose, and prolonged the midazolam elimination half-life by 48% (22–81%) after the oral dose and by 20% (2–40%) after the IV dose. Lapatinib decreased midazolam total clearance by 13% (1–23%), while total bioavailability was increased 23% (4–46%) without changes in apparent volume of distribution or hepatic bioavailability.

Conclusion

These data show that lapatinib caused weak inhibition of gastrointestinal CYP3A4 in vivo. This suggests that oral CYP3A4 drug substrates with a narrow therapeutic index may need dose reduction if lapatinib is to be co-prescribed.

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The effects of lapatinib on CYP3A metabolism of midazolam in patients with advanced cancer

Abstract

Purpose

The potential inhibition of CYP3A4 by lapatinib was studied using midazolam as a probe substrate in patients with cancer.

Methods

This was a partially randomized, 4-period, 4-sequence, 4-treatment, cross-over study in 24 patients with advanced cancer. Single 1-mg IV and 3-mg oral doses of midazolam were given 2 days apart, in a partially random order, on study days 1, 3, 9, and 11. Lapatinib 1500-mg was administered orally once daily on study days 4 through 11. Midazolam plasma concentrations were measured up to 24-h post dosing, and lapatinib plasma concentrations measured prior to each midazolam dose.

Results

Lapatinib increased the geometric mean (95% CIs) midazolam AUC_(o−∞) by 45% (31–60%) after the oral dose and by 14% (0–29%) after the IV dose, and prolonged the midazolam elimination half-life by 48% (22–81%) after the oral dose and by 20% (2–40%) after the IV dose. Lapatinib decreased midazolam total clearance by 13% (1–23%), while total bioavailability was increased 23% (4–46%) without changes in apparent volume of distribution or hepatic bioavailability.

Conclusion

These data show that lapatinib caused weak inhibition of gastrointestinal CYP3A4 in vivo. This suggests that oral CYP3A4 drug substrates with a narrow therapeutic index may need dose reduction if lapatinib is to be co-prescribed.

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Location, Location, Location: Spatio-Temporal Cues That Define the Cell of Origin in Melanoma

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Maria S. Soengas, E. Elizabeth Patton
It is unclear whether melanoma initiates from mature melanocytes or stem cell precursors. In this issue of Cell Stem Cell, Moon et al. (2017) and Köhler et al. (2017) use in vivo lineage tracing to demonstrate that these two possibilities may occur downstream of the same pro-tumorigenic lesions, depending on environmental factors or the anatomical location.

Teaser

It is unclear whether melanoma initiates from mature melanocytes or stem cell precursors. In this issue of Cell Stem Cell, Moon et al. (2017) and Köhler et al. (2017) use in vivo lineage tracing to demonstrate that these two possibilities may occur downstream of the same pro-tumorigenic lesions, depending on environmental factors or the anatomical location.


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Vitamin C: C-ing a New Way to Fight Leukemia

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Katharina Schönberger, Nina Cabezas-Wallscheid
Metabolic cues and (epi-)genetic factors are emerging regulators of hematopoietic stem cell (HSC) potency. Two new studies in Nature and Cell, from Agathocleous et al. (2017) and Cimmino et al. (2017), respectively, show that vitamin C regulates HSC function and suppresses leukemogenesis by modulating Tet2 activity.

Teaser

Metabolic cues and (epi-)genetic factors are emerging regulators of hematopoietic stem cell (HSC) potency. Two new studies in Nature and Cell, from Agathocleous et al. (2017) and Cimmino et al. (2017), respectively, show that vitamin C regulates HSC function and suppresses leukemogenesis by modulating Tet2 activity.


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At Last: Gene Editing in Human Embryos to Understand Human Development

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Albert Ruzo, Ali H. Brivanlou
Our understanding of early human development is typically based on inference from animal models, which may not fully recapitulate human embryonic features. As proof of concept, Fogarty et al. (2017) used CRISPR/Cas9 to genetically ablate the OCT4 gene in human preimplantation embryos and found key differences from its function in model systems.

Teaser

Our understanding of early human development is typically based on inference from animal models, which may not fully recapitulate human embryonic features. As proof of concept, Fogarty et al. (2017) used CRISPR/Cas9 to genetically ablate the OCT4 gene in human preimplantation embryos and found key differences from its function in model systems.


http://ift.tt/2z7N2d5

EMPhasis on Mutant Microglia: Dysregulation of Brain Sentinels Induces Neurodegeneration

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Bettina Schreiner, Melanie Greter
Reactive microglia are often implicated in the pathology of neurodegenerative disease. In a recent study in Nature, Mass et al. (2017) demonstrate that targeted mutation of Braf in early erythro-myeloid precursors (EMPs) causes histiocytosis-associated late onset neurodegeneration driven by activated microglia.

Teaser

Reactive microglia are often implicated in the pathology of neurodegenerative disease. In a recent study in Nature, Mass et al. (2017) demonstrate that targeted mutation of Braf in early erythro-myeloid precursors (EMPs) causes histiocytosis-associated late onset neurodegeneration driven by activated microglia.


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Human Trials of Stem Cell-Derived Dopamine Neurons for Parkinson’s Disease: Dawn of a New Era

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Roger A. Barker, Malin Parmar, Lorenz Studer, Jun Takahashi
Stem cell-based therapies for Parkinson's disease are moving into a new and exciting era, with several groups pursuing clinical trials with pluripotent stem cell (PSC)-derived dopamine neurons. As many groups have ongoing or completed GMP-level cell manufacturing, we highlight key clinical translation considerations from our recent fourth GForce-PD meeting.

Teaser

Stem cell-based therapies for Parkinson's disease are moving into a new and exciting era, with several groups pursuing clinical trials with pluripotent stem cell (PSC)-derived dopamine neurons. As many groups have ongoing or completed GMP-level cell manufacturing, we highlight key clinical translation considerations from our recent fourth GForce-PD meeting.


http://ift.tt/2z6YLc1

Neural Circuits Serve as Periscopes for NSCs

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Nannan Guo, Amar Sahay
Neural stem cells (NSCs) within the hippocampal niche integrate local cues, such as activity of inhibitory interneurons, into their homeostatic fate choices. Now in Cell Stem Cell, Bao et al. (2017) describe how these local interneurons relay signals from distal brain regions to govern NSC quiescence and activation.

Teaser

Neural stem cells (NSCs) within the hippocampal niche integrate local cues, such as activity of inhibitory interneurons, into their homeostatic fate choices. Now in Cell Stem Cell, Bao et al. (2017) describe how these local interneurons relay signals from distal brain regions to govern NSC quiescence and activation.


http://ift.tt/2h5Q7U9

Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Richard A. Morgan, David Gray, Anastasia Lomova, Donald B. Kohn
The use of allogeneic hematopoietic stem cells (HSCs) to treat genetic blood cell diseases has become a clinical standard but is limited by the availability of suitable matched donors and potential immunologic complications. Gene therapy using autologous HSCs should avoid these limitations and thus may be safer. Progressive improvements in techniques for genetic correction of HSCs, by either vector gene addition or gene editing, are facilitating successful treatments for an increasing number of diseases. We highlight the progress, successes, and remaining challenges toward the development of HSC gene therapies and discuss lessons they provide for the development of future clinical stem cell therapies.

Teaser

Morgan et al. discuss the progress, successes, and remaining challenges toward the development of hematopoietic stem cell gene therapies and highlight lessons learned and how they can inform the development of future clinical stem cell therapies.


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Targeting Glioma Stem Cell-Derived Pericytes Disrupts the Blood-Tumor Barrier and Improves Chemotherapeutic Efficacy

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Wenchao Zhou, Cong Chen, Yu Shi, Qiulian Wu, Ryan C. Gimple, Xiaoguang Fang, Zhi Huang, Kui Zhai, Susan Q. Ke, Yi-Fang Ping, Hua Feng, Jeremy N. Rich, Jennifer S. Yu, Shideng Bao, Xiu-Wu Bian
The blood-tumor barrier (BTB) is a major obstacle for drug delivery to malignant brain tumors such as glioblastoma (GBM). Disrupting the BTB is therefore highly desirable but complicated by the need to maintain the normal blood-brain barrier (BBB). Here we show that targeting glioma stem cell (GSC)-derived pericytes specifically disrupts the BTB and enhances drug effusion into brain tumors. We found that pericyte coverage of tumor vasculature is inversely correlated with GBM patient survival after chemotherapy. Eliminating GSC-derived pericytes in xenograft models disrupted BTB tight junctions and increased vascular permeability. We identified BMX as an essential factor for maintaining GSC-derived pericytes. Inhibiting BMX with ibrutinib selectively targeted neoplastic pericytes and disrupted the BTB, but not the BBB, thereby increasing drug effusion into established tumors and enhancing the chemotherapeutic efficacy of drugs with poor BTB penetration. These findings highlight the clinical potential of targeting neoplastic pericytes to significantly improve treatment of brain tumors.

Graphical abstract

Teaser

The blood-brain barrier (BBB) blocks entry of harmful materials into normal brains, but the blood-tumor barrier (BTB) prevents anti-cancer drugs from penetrating GBM tumors. Targeting GSC-derived neoplastic pericytes selectively disrupted the BTB, but not BBB, and potently enhanced drug delivery to effectively improve GBM treatment.


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Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Hechen Bao, Brent Asrican, Weidong Li, Bin Gu, Zhexing Wen, Szu-Aun Lim, Issac Haniff, Charu Ramakrishnan, Karl Deisseroth, Benjamin Philpot, Juan Song
The quiescence of adult neural stem cells (NSCs) is regulated by local parvalbumin (PV) interneurons within the dentate gyrus (DG). Little is known about how local PV interneurons communicate with distal brain regions to regulate NSCs and hippocampal neurogenesis. Here, we identify GABAergic projection neurons from the medial septum (MS) as the major afferents to dentate PV interneurons. Surprisingly, dentate PV interneurons are depolarized by GABA signaling, which is in sharp contrast to most mature neurons hyperpolarized by GABA. Functionally, these long-range GABAergic inputs are necessary and sufficient to maintain adult NSC quiescence and ablating them leads to NSC activation and subsequent depletion of the NSC pool. Taken together, these findings delineate a GABAergic network involving long-range GABAergic projection neurons and local PV interneurons that couples dynamic brain activity to the neurogenic niche in controlling NSC quiescence and hippocampal neurogenesis.

Graphical abstract

Teaser

Bao et al. demonstrate that long-range GABAergic projections from the medial septum control adult hippocampal neurogenesis through depolarizing GABA signaling onto local PV interneurons. Functionally, these long-range inputs are required for maintaining NSC quiescence and ablating them depletes the NSC pool and impairs neurogenesis.


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TGF-β-Induced Quiescence Mediates Chemoresistance of Tumor-Propagating Cells in Squamous Cell Carcinoma

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Jessie A. Brown, Yoshiya Yonekubo, Nicole Hanson, Ana Sastre-Perona, Alice Basin, Julie A. Rytlewski, Igor Dolgalev, Shane Meehan, Aristotelis Tsirigos, Slobodan Beronja, Markus Schober
Squamous cell carcinomas (SCCs) are heterogeneous tumors sustained by tumor-propagating cancer cells (TPCs). SCCs frequently resist chemotherapy through still unknown mechanisms. Here, we combine H2B-GFP-based pulse-chasing with cell-surface markers to distinguish quiescent from proliferative TPCs within SCCs. We find that quiescent TPCs resist DNA damage and exhibit increased tumorigenic potential in response to chemotherapy, whereas proliferative TPCs undergo apoptosis. Quiescence is regulated by TGF-β/SMAD signaling, which directly regulates cell-cycle gene transcription to control a reversible G1 cell-cycle arrest, independent of p21^CIP function. Indeed, genetic or pharmacological TGF-β inhibition increases the susceptibility of TPCs to chemotherapy because it prevents entry into a quiescent state. These findings provide direct evidence that TPCs can reversibly enter a quiescent, chemoresistant state and thereby underscore the need for combinatorial approaches to improve treatment of chemotherapy-resistant SCCs.

Graphical abstract

Teaser

Heterogeneous tumors, such as squamous cell carcinomas, are often chemoresistant and comprise subpopulations of poorly characterized tumor-propagating cancer cells (TPCs). Brown et al. demonstrate that TPCs reversibly enter a quiescent, chemoresistant state and inhibiting TGF-β signaling can increase their susceptibility to chemotherapy by preventing cell-cycle withdrawal in tumors.


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An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells

Publication date: 2 November 2017
Source:Cell Stem Cell, Volume 21, Issue 5
Author(s): Rebecca V. Berrens, Simon Andrews, Dominik Spensberger, Fátima Santos, Wendy Dean, Poppy Gould, Jafar Sharif, Nelly Olova, Tamir Chandra, Haruhiko Koseki, Ferdinand von Meyenn, Wolf Reik
Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs. Inhibition of Dicer or Ago2 expression revealed that small RNAs are involved in an immediate response to demethylation-induced transposon activation, while the deposition of repressive histone marks follows as a chronic response. In vivo, we also found TE-specific endosiRNAs present during primordial germ cell development. Our results suggest that antisense TE transcription is a "trap" that elicits an endosiRNA response to restrain acute transposon activity during epigenetic reprogramming in the mammalian germline.

Graphical abstract

Teaser

In this issue of Cell Stem Cell, Berrens et al. report the control of transposable elements by endosiRNAs during global DNA demethylation induced in mouse embryonic stem cells. The study uncovered an "immediate" repression of transposons accomplished by endosiRNAs followed by their "chronic/long-term" silencing by repressive histone modifications.


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The effects of lapatinib on CYP3A metabolism of midazolam in patients with advanced cancer

Abstract

Purpose

The potential inhibition of CYP3A4 by lapatinib was studied using midazolam as a probe substrate in patients with cancer.

Methods

This was a partially randomized, 4-period, 4-sequence, 4-treatment, cross-over study in 24 patients with advanced cancer. Single 1-mg IV and 3-mg oral doses of midazolam were given 2 days apart, in a partially random order, on study days 1, 3, 9, and 11. Lapatinib 1500-mg was administered orally once daily on study days 4 through 11. Midazolam plasma concentrations were measured up to 24-h post dosing, and lapatinib plasma concentrations measured prior to each midazolam dose.

Results

Lapatinib increased the geometric mean (95% CIs) midazolam AUC_(o−∞) by 45% (31–60%) after the oral dose and by 14% (0–29%) after the IV dose, and prolonged the midazolam elimination half-life by 48% (22–81%) after the oral dose and by 20% (2–40%) after the IV dose. Lapatinib decreased midazolam total clearance by 13% (1–23%), while total bioavailability was increased 23% (4–46%) without changes in apparent volume of distribution or hepatic bioavailability.

Conclusion

These data show that lapatinib caused weak inhibition of gastrointestinal CYP3A4 in vivo. This suggests that oral CYP3A4 drug substrates with a narrow therapeutic index may need dose reduction if lapatinib is to be co-prescribed.

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Temporal and spatial dose distribution of radiation pneumonitis after concurrent radiochemotherapy in stage III non-small cell cancer patients

Radiation pneumonitis (RP) is the most common subacute side effect after concurrent chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer. Several clinical and dose-volume (DV) parameters are...

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Preoperative relative cerebral blood volume analysis in gliomas predicts survival and mitigates risk of biopsy sampling error

Abstract

Appropriate management of adult gliomas requires an accurate histopathological diagnosis. However, the heterogeneity of gliomas can lead to misdiagnosis and undergrading, especially with biopsy. We evaluated the role of preoperative relative cerebral blood volume (rCBV) analysis in conjunction with histopathological analysis as a predictor of overall survival and risk of undergrading. We retrospectively identified 146 patients with newly diagnosed gliomas (WHO grade II–IV) that had undergone preoperative MRI with rCBV analysis. We compared overall survival by histopathologically determined WHO tumor grade and by rCBV using Kaplan–Meier survival curves and the Cox proportional hazards model. We also compared preoperative imaging findings and initial histopathological diagnosis in 13 patients who underwent biopsy followed by subsequent resection. Survival curves by WHO grade and rCBV tier similarly separated patients into low, intermediate, and high-risk groups with shorter survival corresponding to higher grade or rCBV tier. The hazard ratio for WHO grade III versus II was 3.91 (p = 0.018) and for grade IV versus II was 11.26 (p < 0.0001) and the hazard ratio for each increase in 1.0 rCBV units was 1.12 (p < 0.002). Additionally, 3 of 13 (23%) patients initially diagnosed by biopsy were upgraded on subsequent resection. Preoperative rCBV was elevated at least one standard deviation above the mean in the 3 upgraded patients, suggestive of undergrading, but not in the ten concordant diagnoses. In conclusion, rCBV can predict overall survival similarly to pathologically determined WHO grade in patients with gliomas. Discordant rCBV analysis and histopathology may help identify patients at higher risk for undergrading.

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Assuming the Role of NCI Director: Working to Accelerate Progress

Norman Sharpless, M.D., discusses his appointment as the director of the National Cancer Institute and his plans for continuing NCI's long tradition of research excellence and commitment to improving people's lives.

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Accurate Evaluation of Tumour Necrosis in the Preoperative Period: A New Challenge: In Reply

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Refining Tumor Resection Techniques for Managing Inferior Pole Breast Malignancies

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Comment on: Need for Differentiating Diabetes-Specific Mortality from Total Mortality when Comparing Metformin with Insulin Regarding Cancer Survival

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Temporal and spatial dose distribution of radiation pneumonitis after concurrent radiochemotherapy in stage III non-small cell cancer patients

Radiation pneumonitis (RP) is the most common subacute side effect after concurrent chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer. Several clinical and dose-volume (DV) parameters are...

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Comparison of MRI sequences in ideal fiducial maker-based radiotherapy for prostate cancer

Publication date: November–December 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 6
Author(s): Osamu Tanaka, Hisao Komeda, Mitsuyoshi Hattori, Shigeki Hirose, Eiichi Yama, Masayuki Matsuo
AimProstate contouring using CT alone is difficult. To overcome the uncertainty, CT/MRI registration using a fiducial marker is generally performed. However, visualization of the marker itself can be difficult with MRI. This study aimed to determine the optimal MRI pulse sequence for defining the marker as well as the prostate outline among five sequences.Materials and methodsA total of 21 consecutive patients with prostate cancer were enrolled. Two gold fiducial markers were placed before CT/MRI examination. We used the following five sequences: T1-weighted spin-echo (T1WI; TR/TE, 400–650/8ms); T2-weighted fast spin-echo (T2WI; 4000/80); T2*-2D-weighted gradient echo (T2*2D; 700/18); T2*-3D-weighted gradient echo (T2*3D; TR/TE1/deltaTE, 37/14/7.3); and contrast-enhanced T1-weighted spin-echo (CE-T1WI; 400–650/8). Qualitative image analysis of the sequences was performed by three observers. These observers subjectively scored all images on a scale of 1–3 (1=unclear, 2=moderate, 3=well visualized). A higher score indicated better visualization.ResultsT2WI was significantly superior to the other sequences in terms of prostate definition. T2*2D and T2*3D were strongly superior to the other sequences and were significantly superior in terms of fiducial marker definition.ConclusionsT2*2D and T2*3D are superior to the other sequences for prostate contouring and marker identification. Therefore, we recommend initial T2*3D and T2*2D examinations.



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Preoperative relative cerebral blood volume analysis in gliomas predicts survival and mitigates risk of biopsy sampling error

Abstract

Appropriate management of adult gliomas requires an accurate histopathological diagnosis. However, the heterogeneity of gliomas can lead to misdiagnosis and undergrading, especially with biopsy. We evaluated the role of preoperative relative cerebral blood volume (rCBV) analysis in conjunction with histopathological analysis as a predictor of overall survival and risk of undergrading. We retrospectively identified 146 patients with newly diagnosed gliomas (WHO grade II–IV) that had undergone preoperative MRI with rCBV analysis. We compared overall survival by histopathologically determined WHO tumor grade and by rCBV using Kaplan–Meier survival curves and the Cox proportional hazards model. We also compared preoperative imaging findings and initial histopathological diagnosis in 13 patients who underwent biopsy followed by subsequent resection. Survival curves by WHO grade and rCBV tier similarly separated patients into low, intermediate, and high-risk groups with shorter survival corresponding to higher grade or rCBV tier. The hazard ratio for WHO grade III versus II was 3.91 (p = 0.018) and for grade IV versus II was 11.26 (p < 0.0001) and the hazard ratio for each increase in 1.0 rCBV units was 1.12 (p < 0.002). Additionally, 3 of 13 (23%) patients initially diagnosed by biopsy were upgraded on subsequent resection. Preoperative rCBV was elevated at least one standard deviation above the mean in the 3 upgraded patients, suggestive of undergrading, but not in the ten concordant diagnoses. In conclusion, rCBV can predict overall survival similarly to pathologically determined WHO grade in patients with gliomas. Discordant rCBV analysis and histopathology may help identify patients at higher risk for undergrading.

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Accurate Evaluation of Tumour Necrosis in the Preoperative Period: A New Challenge: In Reply

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Refining Tumor Resection Techniques for Managing Inferior Pole Breast Malignancies

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Comment on: Need for Differentiating Diabetes-Specific Mortality from Total Mortality when Comparing Metformin with Insulin Regarding Cancer Survival

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LOC285629 regulates cell proliferation and motility in colorectal cancer cells

Abstract

Purpose

Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC.

Method

Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler.

Results

Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal–Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K.

Conclusion

Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.

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Non-invasively predicting differentiation of pancreatic cancer through comparative serum metabonomic profiling

Abstract

Background

The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy.

Methods

By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using ¹H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight.

Results

An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation.

Conclusion

The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively.

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Preoperative relative cerebral blood volume analysis in gliomas predicts survival and mitigates risk of biopsy sampling error

Abstract

Appropriate management of adult gliomas requires an accurate histopathological diagnosis. However, the heterogeneity of gliomas can lead to misdiagnosis and undergrading, especially with biopsy. We evaluated the role of preoperative relative cerebral blood volume (rCBV) analysis in conjunction with histopathological analysis as a predictor of overall survival and risk of undergrading. We retrospectively identified 146 patients with newly diagnosed gliomas (WHO grade II–IV) that had undergone preoperative MRI with rCBV analysis. We compared overall survival by histopathologically determined WHO tumor grade and by rCBV using Kaplan–Meier survival curves and the Cox proportional hazards model. We also compared preoperative imaging findings and initial histopathological diagnosis in 13 patients who underwent biopsy followed by subsequent resection. Survival curves by WHO grade and rCBV tier similarly separated patients into low, intermediate, and high-risk groups with shorter survival corresponding to higher grade or rCBV tier. The hazard ratio for WHO grade III versus II was 3.91 (p = 0.018) and for grade IV versus II was 11.26 (p < 0.0001) and the hazard ratio for each increase in 1.0 rCBV units was 1.12 (p < 0.002). Additionally, 3 of 13 (23%) patients initially diagnosed by biopsy were upgraded on subsequent resection. Preoperative rCBV was elevated at least one standard deviation above the mean in the 3 upgraded patients, suggestive of undergrading, but not in the ten concordant diagnoses. In conclusion, rCBV can predict overall survival similarly to pathologically determined WHO grade in patients with gliomas. Discordant rCBV analysis and histopathology may help identify patients at higher risk for undergrading.

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LOC285629 regulates cell proliferation and motility in colorectal cancer cells

Abstract

Purpose

Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC.

Method

Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler.

Results

Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal–Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K.

Conclusion

Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.

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Acute toxicity of image-guided hypofractionated proton therapy for localized prostate cancer

Abstract

Background

Hypofractionated proton therapy (HFPT) is expected to become an effective treatment approach for localized prostate cancer (PCa). The purpose of this study was to evaluate differences in acute toxicity among patients with localized PCa treated with either conventional fractionated proton therapy (CFPT) or HFPT.

Methods

A total of 526 eligible patients treated with proton therapy between February 2013 and May 2016 in three phase II trials were analyzed. We prescribed 74 gray relative biological effectiveness equivalents [Gy (RBE)]/37 fractions for low-risk patients and 78 Gy (RBE)/39 fractions for intermediate- and high-risk patients in the CFPT group (n = 254) and 60 Gy (RBE)/20 fractions for low-risk and 63 Gy (RBE)/21 fractions for intermediate- and high-risk patients in the HFPT group (n = 272). Patients were evaluated for acute toxicity with the Common Terminology Criteria for Adverse Events, version 4.0, and urinary quality-of-life change using the International Prostate Symptom Score (IPSS).

Results

No grade ≥3 acute toxicity was observed in either group. Among acute genitourinary toxicities, grade 2 rates were 15% (n = 38) in CFPT and 5.9% (n = 16) in HFPT (P ≤ 0.001). The median baseline IPSSs of the CFPT and HFPT groups were 7 (0–29) and 6 (0–31), respectively (P = 0.70). One-month post-treatment scores were 9 (0–32) and 11 (0–32), respectively (P = 0.036), and 6-month post-treatment scores were 7 (0–30) and 7 (0–33), respectively (P = 0.88). There were no significant differences in acute gastrointestinal toxicity between the two groups.

Conclusion

Our results demonstrated the safety of HFPT for localized PCa patients in terms of acute toxicity.

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Understanding Mitochondrial Polymorphisms in Cancer

Alterations in mitochondrial DNA (mtDNA) were once thought to be predominantly innocuous to cell growth. Recent evidence suggests that mtDNA undergo naturally occurring alterations, including mutations and polymorphisms, which profoundly affect the cells in which they appear and contribute to a variety of diseases, including cardiovascular disease, diabetes, and cancer. Furthermore, interplay between mtDNA and nuclear DNA has been found in cancer cells, necessitating consideration of these complex interactions for future studies of cancer mutations and polymorphisms. In this issue of Cancer Research, Vivian and colleagues utilize a unique mouse model, called Mitochondrial Nuclear eXchange mice, that contain the nuclear DNA from one inbred mouse strain, and the mtDNA from a different inbred mouse strain to examine the genome-wide nuclear DNA methylation and gene expression patterns of brain tissue. Results demonstrated there were alterations in nuclear DNA expression and DNA methylation driven by mtDNA. These alterations may impact disease pathogenesis. In light of these results, in this review, we highlight alterations in mtDNA, with a specific focus on polymorphisms associated with cancer susceptibility and/or prognosis, mtDNA as cancer biomarkers, and considerations for investigating the role of mtDNA in cancer progression for future studies. Cancer Res; 77(22); 1–9. ©2017 AACR.

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LOC285629 regulates cell proliferation and motility in colorectal cancer cells

Abstract

Purpose

Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC.

Method

Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler.

Results

Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal–Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K.

Conclusion

Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.

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Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer

This review describes the pivotal roles of cell-cycle and checkpoint regulators and discusses development of specific cell-cycle inhibitors for therapeutic use for pediatric cancer. The mechanism of action as well as the safety and tolerability of drugs in pediatric patients, including compounds that target CDK4/CDK6 (palbociclib, ribociclib, and abemaciclib), aurora kinases (AT9283 and MLN8237), Wee1 kinase (MK-1775), KSP (ispinesib), and tubulin (taxanes, vinca alkaloids), are presented. The design of mechanism-based combinations that exploit the cross-talk of signals activated by cell-cycle arrest, as well as pediatric-focused drug development, are critical for the advancement of drugs for rare childhood diseases. Cancer Res; 1–10. ©2017 AACR.

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Uncoupling the Oncogenic Engine

Inhibition of oncogenic signaling and correction of aberrant metabolic processes may be key paradigms to eliminate cancer cells. The high incidence of activating RAS mutations and hyperactivated ERK1/2 signaling observed in many human tumors and the lack of effective targeted therapies to elicit long-term inhibition of the RAS-ERK1/2 signaling pathway add to the importance of discovering novel strategies to treat malignancies characterized by elevated RAS-ERK1/2 signaling. In this review, we describe connections between oncogenic signaling and cancer cell metabolism and how these links may be exploited for novel modern molecular medicine approaches. Cancer Res; 77(22); 1–5. ©2017 AACR.

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Adaptive evolution of the GDH2 allosteric domain promotes gliomagenesis by resolving IDH1R132H induced metabolic liabilities

Hot-spot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malignant gliomas, IDH1R132H expression induces widespread metabolic reprogramming, possibly requiring compensatory mechanisms to sustain the normal biosynthetic requirements of actively proliferating tumor cells. We used genetically engineered mouse models of glioma and quantitative metabolomics to investigate IDH1R132H-dependent metabolic reprogramming and its potential to induce biosynthetic liabilities that can be exploited for glioma therapy. In gliomagenic neural progenitor cells, IDH1R132H expression increased the abundance of dipeptide metabolites, depleted key tricarboxylic acid (TCA) cycle metabolites, and slowed progression of murine gliomas. Notably, expression of glutamate dehydrogenase GDH2, a hominoid-specific enzyme with relatively restricted expression to the brain, was critically involved in compensating for IDH1R132H-induced metabolic alterations and promoting IDH1R132H glioma growth. Indeed, we found that recently evolved amino acid substitutions in the GDH2 allosteric domain conferred its non-redundant, glioma-promoting properties in the presence of IDH1 mutation. Our results indicate that among the unique roles for GDH2 in the human forebrain is its ability to limit IDH1R132H-mediated metabolic liabilities, thus promoting glioma growth in this context. Results from this study raise the possibility that GDH2-specific inhibition may be a viable therapeutic strategy for gliomas with IDH mutations.

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Deletion of neuropilin 1 from microglia or bone marrow-derived macrophages slows glioma progression

Glioma-associated microglia and macrophages (GAM) which infiltrate high-grade gilomas represent constitute a major cellular component of these lesions. GAM behavior is influenced by tumor-derived cytokines that suppress initial anti-tumorigenic properties, causing them to support tumor growth and to convert and suppress adaptive immune responses to the tumor. Mice which lack the transmembrane receptor neuropilin-1 (Nrp1) which modulates GAM immune polarization exhibit a decrease in glioma volumes and neoangiogenesis and an increase in anti-tumorigenic GAM infiltrate. Here we show that replacing the peripheral macrophage populations of wild type mice with Nrp1-depleted bone marrow-derived macrophages (BMDM) confers resistance to the development of glioma. This resistance occurred in a similar fashion seen in mice in which all macrophages lacked Nrp1 expression. Tumors had decreased volumes, decreased vascularity, increased CTL infiltrate, and Nrp1-depleted BMDM adopted a more anti-tumorigenic phenotype relative to wild type GAM within the tumors. Mice with Nrp1-deficient microglia and wild type peripheral macrophages showed resistance to glioma development and had higher microglial infiltrate than mice with wild type GAM. Our findings show how manipulating Nrp1 in either peripheral macrophages or microglia reprograms their phenotype and relieve their pathogenic roles in tumor neovascularization and immunosuppression.

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Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer

Abstract

Background

Our goal was to compare the survival advantage of tamoxifen (TAM) and aromatase inhibitor (AI) in female (FBC) and male breast cancer (MBC).

Patients and methods

We performed a retrospective study of 2785 FBC and 257 MBC patients treated with hormonal therapy.

Results

The median follow-up was 106 months (range 3–151 months) and 42 months (range 2–115 months) for FBC and MBC, respectively. The patients were divided into two groups according to the hormonal therapy used: TAM-treated and AI-treated. MBC was characterized by older age, advanced tumor stage, and higher rate of lymph node metastases, in comparison with FBC. Matching analysis was performed using six prognostic criteria: patient age, tumor stage, tumor grade, lymph node status, human epidermal growth factor receptor (HER2) status, and administration of chemotherapy. The female and male patients were matched 2:1. In this analysis, 316 women and 158 men treated with TAM, and 60 women and 30 men treated with AI, were included. The overall survival (OS) was estimated by the Kaplan–Meier method and was compared between FBC and MBC. TAM-treated FBC and MBC patients had similar 5-year OS, 85.1 and 89.2%, respectively (p = 0.972). Notably, FBC patients treated with AI had significantly greater 5-year OS (85.0%) in comparison with AI-treated MBC patients (5-year OS of 73.3%; p = 0.028).

Conclusions

The OS of TAM-treated patients with MBC was similar to the OS of TAM-treated FBC patients, whereas AI treatment is associated with poorer survival of MBC patients.

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