High-Magnification Microscopy Visualizes Tumor Blood Vessels in Real Time

Researchers have adapted a high-magnification technique for viewing body structures at the cellular level so that they can visualize blood vessels in human tumors in real time.

Using the technique, called intravital microscopy (IVM), they found that approximately half of blood vessels in tumors in patients with melanoma had no blood flow and that tumor blood vessels were much larger than would have been anticipated from prior studies.

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Inhibition of E-selectin expression on the surface of endothelial cells inhibits hepatocellular carcinoma growth by preventing tumor angiogenesis

Abstract

Purpose

Interactions between endothelial and tumor cells via E-selectin and sialyl Lewis x (sLex) have been suggested to play a significant role in the development of metastasis and tumor growth. In this work, we tested whether inhibition of E-selectin expression on the surface of endothelial cells might impair endothelial/tumor cells interactions and tumor growth of hepatocarcinoma cells in vitro and in vivo.

Methods

We used HepG2 cells that highly express sLex antigens and HuH7 cells that do not express sLex. Inhibition of E-selectin expression on the surface of endothelial cells was obtained by using cimetidine and amiloride treatment.

Results

Cimetidine and amiloride inhibited, respectively, by 20 and 64 % E-selectin expression by activated endothelial cells and significantly subsequent adhesion of HepG2 cells to activated endothelial cells. Subcutaneous injection of cimetidine or amiloride resulted in a significant inhibition of HepG2 cells tumor growth in nu/nu mice but not of HuH7 cells. Thus, cimetidine and amiloride administration led to an inhibition of 57 and 75 % of HepG2 tumor growth in vivo, respectively. This effect was associated with an inhibition of vasculogenesis as demonstrated by anti-CD31 immunostaining.

Conclusion

Inhibition of E-selectin expression allows an anti-tumoral effect on sLex-expressing HCC tumors in vivo. This suggests that interactions between HCC cells and endothelial cells through sLex antigens and E-selectin might be a target for treatment of HCC. Further studies might evaluate the clinical impact of cimetidine and amiloride in the treatment of HCC patients alone or in combination with other anti-tumoral agents.

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Pharmacokinetics of high-dose methotrexate in infants aged less than 12 months treated for aggressive brain tumors

Abstract

Purpose

In infants aged less than 12 months, there are few data on pharmacokinetics of high-dose methotrexate (MTX) for brain tumors at the dose of 8 g/m². Consolidated knowledges are present only with the dose of 5 g/m² in acute lymphoblastic leukemia.

Methods

We collected data on 8 infants at the time of their first treatment with high-dose MTX, 8 g/m², to evaluate the pharmacokinetic profile. All children had a dose adjustment with a weight-based prescription (1 m² = 30 kg).

Results

The median age was 4.5 months (range 0–9). The median weight was 5.63 kg (range 3.12–9.0). The median steady-state MTX concentration at the end of 6-hr infusion was 486 µM/L (range 227–790). The median systemic MTX clearance was 4.14 L/h/m² (range 1.98–9.35). The median MTX concentration after 24 h from the beginning of infusion was 3.29 µM/L (range 1.14–100.44). Three (37.5 %) patients had a delayed elimination of MTX (delayed early, delayed late, or total delayed: one for each). These altered elimination occurred principally in children weighing less than 4 kg (p: 0.0179). Moreover, a systemic MTX clearance at the end of infusion minor than 3 L/h/m² can predict a delayed elimination (p: 0.0179). Patients with altered elimination underwent rescue measures (leucovorin supplement and/or exchange transfusion).

Conclusions

Our data suggest that a higher dose of MTX for the treatment of aggressive brain tumors in early infants had an acceptable pharmacokinetic profile. Greater attention must be used in the treatment of children weighing less than 4 kg.

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Is the prevalence of colonic neuroendocrine tumors increased in patients with inflammatory bowel disease?

Abstract

Inflammatory bowel disease (IBD) patients may bear an increased neuroendocrine tumor (NET) risk. These tumors are mostly reported as coincidental findings during surgery. We aimed to determine the prevalence of colonic NET in a Dutch nationwide IBD cohort and calculate the prevalence rate ratios (PRR) compared to the general Dutch population. Our second aim was to investigate whether a high bowel surgery rate in IBD could result in a high PRR for NET.

The Dutch Pathology Registry (PALGA) was searched to identify all IBD patients with colonic NET in The Netherlands between 1991 and 2011. We determined the prevalence and PRR of colonic NET in a 20-year period. For our second aim, we compared NET prevalence in colonic resection specimens between IBD cases and non-IBD controls (diverticulitis and ischemia).

We identified 51 IBD patients who developed colonic NET resulting in a prevalence of 60.4 - 89.3 per 100 000 patients in a 20-year period with a PRR of 2.8 - 4.1. However, adjusted for resection type, sex and age, a higher NET prevalence was shown in diverticulitis (OR 5.52, 95% CI 3.47 - 8.78) and ischemia (OR 1.97, 95% CI 1.09 - 3.58) compared to IBD.

Our key finding is that NET are more prevalent in IBD patients compared to the general population (PRR 2.8 - 4.1). This might be attributed to a high rate of incidental NET as IBD patients frequently undergo intestinal surgery. A lower adjusted NET prevalence in colonic resection specimens for IBD compared to ischemia and diverticulitis supports this hypothesis. This article is protected by copyright. All rights reserved.

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The impact of breast cancer-specific birth-cohort effects among younger and older Chinese populations

Abstract

Historically low breast cancer incidence rates among Asian women have risen worldwide; purportedly due to the adoption of a 'Western' life style among younger generations (i.e., the more recent birth-cohorts). However, no study has simultaneously compared birth-cohort effects between both younger and older women in different Asian and Western populations. Using cancer registry data from rural and urban China, Singapore, and the United States (1990-2008), we estimated age-standardized incidence rates (ASR), annual percentage change (EAPC) in the ASR, net drifts, birth-cohort specific incidence rates and cohort rate ratios (CRR). Younger (30-49 years, 1943-1977 birth-cohorts) and older women (50-79 years; 1913-1957 birth-cohorts) were assessed separately. CRRs among Chinese populations were estimated using birth-cohort specific rates with US non-Hispanic white women (NHW) serving as the reference population with an assigned CRR of 1.0. We observed higher EAPCs and net drifts among those Chinese populations with lower ASRs. Similarly, we observed the most rapidly increasing cohort-specific incidence rates among those Chinese populations with the lowest baseline CRRs. Both trends were more significant among older than younger women. Average CRRs were 0.06∼0.44 among older and 0.18∼0.81 among younger women. Rapidly rising cohort specific rates have narrowed the historic disparity between Chinese and US NHW breast cancer populations particularly in regions with the lowest baseline rates and among older women. Future analytic studies are needed to investigate risk factors accounting for the rapid increase of breast cancer among older and younger women separately in Asian populations. This article is protected by copyright. All rights reserved.

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Does Graded Prognostic Assessment outperform Recursive Partitioning Analysis in patients with moderate prognosis brain metastases?

CNS Oncology Ahead of Print.


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Does valproic acid affect tumor growth and improve survival in glioblastomas?

CNS Oncology Ahead of Print.


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Fatigue among patients with brain tumors

CNS Oncology Ahead of Print.


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The Result of Multiple I-131 Treatments on the Effective Half-Life of Retained Radioactivity in Patients Ablated for Differentiated Thyroid Cancer: Possible Evidence for Thyroid Remnant Function Impairment

Cancer Biotherapy & Radiopharmaceuticals Mar 2016, Vol. 31, No. 2: 58-64.


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Antidifferentiation Noncoding RNA Regulates the Proliferation of Osteosarcoma Cells

Cancer Biotherapy & Radiopharmaceuticals Mar 2016, Vol. 31, No. 2: 52-57.


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Complete Remission of Unresectable Hepatocellular Carcinoma After Combined Sorafenib and Adjuvant Yttrium-90 Radioembolization

Cancer Biotherapy & Radiopharmaceuticals Mar 2016, Vol. 31, No. 2: 65-69.


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An automated electronic system for radiation treatment plan peer review reduces missed reviews at a large, high-volume academic center

Publication date: Available online 16 March 2016
Source:Practical Radiation Oncology
Author(s): Peter E. Gabriel, Kristina D. Woodhouse, Alexander Lin, Jarod C. Finlay, Richard B. Young, Edna Volz, Stephen M. Hahn, James M. Metz, Amit Maity
BackgroundAssuring quality in cancer care through peer review has become increasingly important in radiation oncology. In 2012, the Department of Radiation Oncology at XX implemented an automated electronic system for radiation treatment plan peer review. The purpose of this study was to compare the overall impact of this electronic system to our previous manual, paper-based system.MethodsIn an effort to improve management, an automated electronic system for case finding and documentation of review was developed and implemented. The rates of missed initial reviews, late reviews, and missed re-reviews were compared for the pre- vs. post-electronic system cohorts using Pearson's chi-squared test and relative risk. Major and minor changes or recommendations were documented and shared with the assigned clinical provider.ResultsThe overall rate of missed reviews was 7.6% (38/500) prior to system implementation vs. 0.4% (28/6985) under the electronic system (p<0.001). In terms of relative risk, courses were 19.0 times (95% CI 11.8-30.7) more likely to be missed for initial review prior to the automated system. Missed re-reviews occurred in 23.1% (3/13) of courses in the pre-electronic system cohort and 6.6% (10/152) of courses in the post-electronic system cohort (p = 0.034). Late reviews were more frequent during high travel or major holiday periods. Major changes were recommended in 2.2% and 2.8% in the pre- vs. post-electronic systems, respectively. Minor changes were recommended in 5.3% of all post-electronic cases.ConclusionThe implementation of an automated electronic system for managing peer review in a large, complex department was effective in significantly reducing the number of missed reviews and missed re-reviews when compared to our previous manual system.



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Failure Mode and Effects Analysis in a Dual-Product Microsphere Brachytherapy Environment

Publication date: Available online 16 March 2016
Source:Practical Radiation Oncology
Author(s): Kelly Cooper Younge, Choonik I. Lee, Jean M. Moran, Mary Feng, Paula Novelli, Joann I. Prisciandaro
PurposeWe performed a failure mode and effects analysis (FMEA) during the addition of a new microspheres product into our existing microsphere brachytherapy program to identify areas for safety improvements.Methods and MaterialsA diverse group of team members from the microsphere program participated in the project to create a process map, identify and score failure modes, and discuss programmatic changes to address the highest-ranking items. We developed custom severity ranking scales for staff- and institution-related failure modes to encompass possible risks that may exist outside of patient-based effects.ResultsFor both types of microsphere products, a total of 173 failure mode / effect pairs were identified: 90 for patients, 35 for staff, and 48 for the institution. The SIR-Sphere program was ranked separately from the Therasphere program because of significant differences in workflow during dose calculation, preparation, and delivery. High-ranking failure modes in each category were addressed with programmatic changes.ConclusionThe FMEA aided in identifying potential risk factors in our microsphere program and allowed a theoretically safer and more efficient design of the workflow and quality assurance for both our new SIR-Sphere program and our existing Therasphere program. As new guidelines are made available, and our experience with the SIR-Sphere program increases, we will update the FMEA as an efficient starting point for future improvements.



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Human papillomavirus detection in a “Digital” age

It is increasingly important to identify the presence of human papillomavirus (HPV) in patients with oropharyngeal squamous cell carcinoma, because HPV status is now useful for clinical trial stratification, prognostic determination, diagnosis in patients with neck masses, and identification of the primary tumor site. Therefore, it is important that the technique used for identification be feasible, accurate, reproducible, and cost effective. The authors summarize these aspects of HPV detection and the use of newer digital polymerase chain reaction technology for this purpose. See also pages.

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Detection of human papillomavirus type 16 in oropharyngeal squamous cell carcinoma using droplet digital polymerase chain reaction

BACKGROUND

The incidence of oropharyngeal squamous cell carcinoma caused by oncogenic HPV (HPV-OPSCC) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV-16 E6 and E7 oncoproteins or by cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 (p16) immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. We aimed to validate this method for the detection of HPV-16 E6 and E7 in HPV-OPSCC.

METHODS

Participants were recruited from January 2015-November 2015 at initial presentation to the University of Alberta Head and Neck Oncology Clinic. RNA was extracted, purified and quantified from prospectively collected participant tissues, and ddPCR was performed with fluorescent probes detecting HPV-16 E6 and E7. Results from ddPCR were compared with p16 IHC performed by clinical pathology as standard of care.

RESULTS

Head and neck tissues were prospectively obtained from 68 participants including 29 patients with OPSCC, 29 patients with non-OPSCC and 10 patients without carcinoma. 79.2% of patients with OPSCC were p16 positive. The sensitivity and specificity of ddPCR HPV E6/E7 compared with p16 IHC in OPSCC was 91.3 and 100%, respectively. The amount of target RNA used was ≤1 ng, 20-50 times lower than reported by other for RT-qPCR HPV E6/E7.

CONCLUSIONS

The ddPCR of HPV E6/E7 is a novel and highly specific method of detecting HPV-16 in OPSCC. Cancer 2016. © 2016 American Cancer Society.

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Safety of vemurafenib in patients with BRAF V600 mutated metastatic melanoma: the Spanish experience

Abstract

Objectives

Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAF ^V600 mutated advanced melanoma. We investigated safety, tolerability and efficacy of vemurafenib in Spanish patients participating in that study.

Methods

Patients with previously treated or treatment-naive, unresectable stage IIIC or stage IV, BRAF ^V600 mutation-positive melanoma received vemurafenib 960 mg twice daily until disease progression, unacceptable toxicity, withdrawal of consent or death. The primary endpoint was safety; secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Results

301 Spanish patients were included, 70 % with M1c disease, 22 % with brain metastases and 51 % with prior systemic therapy for metastatic disease. Most frequent adverse events included fatigue (48 %), arthralgia (45 %), rash (41 %), photosensitivity (34 %) and skin neoplasms (21 %). Grade 3/4 adverse events occurred in 156 patients (52 %), including cutaneous squamous cell carcinoma (including keratoacanthoma; 16 %), fatigue (6 %) and arthralgia (5 %). The ORR was 28 % (95 % CI 23–34 %). Responses occurred in patients with brain metastases (18 %), elevated baseline lactate dehydrogenase (19 %) and poor performance status (15 %), and elderly patients (22 %). Median PFS was 5.8 (95 % CI 5.0–6.4) months; median OS was 10.5 (95 % CI 9.5–13.5) months.

Conclusion

Our results for Spanish patients in the vemurafenib safety study indicate similar efficacy and a comparable safety profile in Spanish patients with no new safety signals compared with the overall population. Clinical benefit was demonstrated in poor-prognosis patients and in those with favourable baseline characteristics, suggesting that poor-prognosis patients may also benefit from vemurafenib treatment.

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The role of public policies in reducing smoking prevalence: results from the Michigan SimSmoke tobacco policy simulation model

Abstract

Introduction

Michigan has implemented several of the tobacco control policies recommended by the World Health Organization MPOWER goals. We consider the effect of those policies and additional policies consistent with MPOWER goals on smoking prevalence and smoking-attributable deaths (SADs).

Methods

The SimSmoke tobacco control policy simulation model is used to examine the effect of past policies and a set of additional policies to meet the MPOWER goals. The model is adapted to Michigan using state population, smoking, and policy data starting in 1993. SADs are estimated using standard attribution methods. Upon validating the model, SimSmoke is used to distinguish the effect of policies implemented since 1993 against a counterfactual with policies kept at their 1993 levels. The model is then used to project the effect of implementing stronger policies beginning in 2014.

Results

SimSmoke predicts smoking prevalence accurately between 1993 and 2010. Since 1993, a relative reduction in smoking rates of 22 % by 2013 and of 30 % by 2054 can be attributed to tobacco control policies. Of the 22 % reduction, 44 % is due to taxes, 28 % to smoke-free air laws, 26 % to cessation treatment policies, and 2 % to youth access. Moreover, 234,000 SADs are projected to be averted by 2054. With additional policies consistent with MPOWER goals, the model projects that, by 2054, smoking prevalence can be further reduced by 17 % with 80,000 deaths averted relative to the absence of those policies.

Conclusions

Michigan SimSmoke shows that tobacco control policies, including cigarette taxes, smoke-free air laws, and cessation treatment policies, have substantially reduced smoking and SADs. Higher taxes, strong mass media campaigns, and cessation treatment policies would further reduce smoking prevalence and SADs.

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Residential cancer cluster investigation nearby a Superfund Study Area with trichloroethylene contamination

Abstract

Purpose

Trichloroethylene (TCE) is an industrial solvent associated with liver cancer, kidney cancer, and non-Hodgkin's lymphoma (NHL). It is unclear whether an excess of TCE-associated cancers have occurred surrounding the Middlefield–Ellis–Whisman Superfund site in Mountain View, California. We conducted a population-based cancer cluster investigation comparing the incidence of NHL, liver, and kidney cancers in the neighborhood of interest to the incidence among residents in the surrounding four-county region.

Methods

Case counts and address information were obtained using routinely collected data from the Greater Bay Area Cancer Registry, part of the Surveillance, Epidemiology, and End Results program. Population denominators were obtained from the 1990, 2000, and 2010 US censuses. Standardized incidence ratios (SIRs) with two-sided 99 % confidence intervals (CIs) were calculated for time intervals surrounding the US Censuses.

Results

There were no statistically significant differences between the neighborhood of interest and the larger region for cancers of the liver or kidney. A statistically significant elevation was observed for NHL during one of the three time periods evaluated (1996–2005: SIR = 1.8, 99 % CI 1.1–2.8). No statistically significant NHL elevation existed in the earlier 1988–1995 (SIR = 1.3, 99 % CI 0.5–2.6) or later 2006–2011 (SIR = 1.3, 99 % CI 0.6–2.4) periods.

Conclusion

There is no evidence of an increased incidence of liver or kidney cancer, and there is a lack of evidence of a consistent, sustained, or more recent elevation in NHL occurrence in this neighborhood. This evaluation included existing cancer registry data, which cannot speak to specific exposures incurred by past or current residents of this neighborhood.

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Angiotensin II increases gene expression after selective intra-arterial adenovirus delivery in a rabbit model assessed using in vivo SSTR2-based reporter imaging

Abstract

Background

Gene therapy has been hampered by low expression upon in vivo delivery. Using a somatostatin receptor type 2 (SSTR2)-based reporter, we assessed whether angiotensin II (AII) can improve gene expression by adenovirus upon intra-arterial (IA) delivery in a large animal model.

Methods

A SSTR2-based reporter that can be imaged by a clinically approved radiopharmaceutical was used to assess gene expression. Eight rabbits bearing VX2 tumors in each thigh were randomly injected IA with adenovirus containing a human SSTR2 (Ad-CMV-HA-SSTR2) gene chimera ± AII or control adenovirus containing green fluorescent protein (Ad-CMV-GFP). Three days later, ¹¹¹In-octreotide was given IV after computed tomography (CT) imaging using a clinical CT scanner and intravenous contrast. Tumor uptake of ¹¹¹In-octreotide was evaluated the next day using a clinical gamma camera. Gene expression was normalized to tumor weight and morphology from CT to obtain in vivo biodistribution.

Results

SSTR2-based expression was readily visualized. VX2 tumors infected with Ad-CMV-HA-SSTR2 upon intra-arterial delivery with AII had greater in vivo biodistribution, thus greater gene expression, than those without AII (p < 0.01, n = 6). VX2 tumors infected with Ad-CMV-HA-SSTR2 upon IA delivery had greater biodistribution, thus greater gene expression, than those with the negative control Ad-CMV-GFP (p < 0.02). Similarly, VX2 tumors infected with Ad-CMV-HA-SSTR2 upon IA delivery with AII had greater biodistribution, thus greater gene expression, than those with the negative control Ad-CMV-GFP (p < 0.01).

Conclusions

Angiotensin II improves in vivo gene expression by adenovirus upon intra-arterial delivery and thus may improve gene therapy efficacy. In vivo SSTR2-based reporter imaging can be used to compare methodologies for improving gene expression.

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Advanced squamous cell carcinomas arising from mature cystic teratoma of the ovary: a retrospective case series at the Tohoku Gynecologic Cancer Unit

Abstract

We retrospectively evaluated the clinical characteristics of a rare clinical condition of International Federation of Gynecology and Obstetrics (FIGO) stage III and IV squamous cell carcinomas arising from mature cystic teratoma of the ovary between October 1999 and September 2010 at member institutions of the Tohoku Gynecologic Cancer Unit. A total of nine cases (eight FIGO stage III and one FIGO stage IV) were included in this survey. The patients' median age was 56 years (range 46–74 years), and the median tumor diameter was 140 mm (range 95–250 mm). Five of eight patients were positive for cancer antigen (CA)-125, six of eight were positive for CA19-9, four of seven were positive for the carcinoembryonic antigen, and eight of nine were positive for squamous cell carcinoma antigen. Eight patients received postoperative therapy (five underwent chemotherapy, two underwent concurrent chemoradiotherapy, and one underwent radiation therapy alone). Two patients who received complete surgery and concurrent chemo radiotherapy achieved disease-free survival. The median overall survival was 8.9 months. Univariate analysis showed that both the patients' age (<50 years or ≥50 years) and maximum diameter of the residual tumor (<1 cm or ≥1 cm and none or persistent) did not predict the patients' prognosis. These results suggest that complete surgery should be performed because disease-free survival was observed only in patients with no residual tumor, similar to the previous findings of large number retrospective study.

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Incidence of chemotherapy-induced nausea and vomiting associated with docetaxel and cyclophosphamide in early breast cancer patients and aprepitant efficacy as salvage therapy. Results from the Spanish Breast Cancer Group/2009-02 study

Publication date: May 2016
Source:European Journal of Cancer, Volume 58
Author(s): Antonio Llombart-Cussac, Manuel Ramos, Elsa Dalmau, José A. García-Saenz, Xavier González-Farré, Laura Murillo, Lourdes Calvo, Serafín Morales, Vicente Carañana, Ana González, Luis A. Fernández-Morales, Fernando Moreno, Mª Isabel Casas, Mª del Mar Angulo, Mª Carmen Cámara, Ana I. Garcia-Mace, Eva Carrasco, Carlos Jara-Sánchez
BackgroundDocetaxel–cyclophosphamide (TC) has become a common regimen in moderate-high-risk early breast cancer (EBC), but the incidence of chemotherapy-induced nausea and vomiting (CINV) with this regimen is not well established. This trial investigates the effect of guideline-consistent prophylaxis on CINV related to TC regimen and explores the efficacy of aprepitant among resistant patients.Patients and MethodsThis prospective multicentre study enrolled 212 chemotherapy-naïve EBC patients receiving T-75 mg/m² and C-600 mg/m². Antiemetic therapy on the first cycle consisted of dexamethasone for 3 d plus 5-hydroxytryptamine (5-HT3) antagonists on day 1, according to Multinational Association of Supportive Care in Cancer guidelines. The primary end-point was complete response (CR) (no emesis and no need of rescue treatment within the initial 120 h). Patients failing CR on cycle 1 entered in a single-arm study exploring the efficacy of aprepitant on the second cycle. Patients' diaries and Functional Living Index-Emesis (FLIE) questionnaires were collected in cycles 1 and 2.ResultsAmong the 185 evaluable patients on cycle 1, 161 (87%, 95% confidence interval [CI]: 82.2–91.8) achieved a CR. Twenty-three patients received aprepitant on cycle 2, and 12 reached a CR (52.2%, 95% CI: 31.8–72.6). The absence of CR had a very substantial impact on quality of life on cycles 1 (FLIE before and after: 23.8–38.1, p = 0.0124) and 2 (18.3–42.9, p = 0.0059).ConclusionsGuideline-consistent antiemetic prophylaxis for the TC regimen is associated with a low incidence of CINV. Aprepitant is effective as secondary prevention of CINV and should be considered as rescue therapy in patients treated with moderate emetogenic chemotherapy.



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Nurse and patient characteristics predict communication about complementary and alternative medicine

BACKGROUND

The aim of this study was to identify nurse factors (eg, knowledge, practices, and clinical habits regarding complementary and alternative medicine [CAM] as well as demographic factors) and patient characteristics (eg, age, sex, and treatment status) associated with nurses' CAM inquiry and referral patterns.

METHODS

Baseline data were collected with nurse/patient questionnaires about CAM use and knowledge as part of a multicenter CAM educational clinical trial. Frequencies and nested regression models were used to assess predictors of nurses' inquiries about and referral to CAM therapies.

RESULTS

Six hundred ninety-nine patients participated in the study. For patients, female sex (odds ratio [OR], 1.50; P = .019) and cancer recurrence (OR, 1.45; P = .05) were predictive of nurses' inquiries about and referral to CAM therapies. A total of 175 nurses with a mean age of 45 years and a mean experience of 20 years participated; 79% were staff nurses, and 11% were nurse practitioners. Fifty-three percent asked at least 1 of their last 5 patients about CAM use; 42% referred patients to CAM therapy. Nurses who reported being "somewhat comfortable" (OR, 2.70; P = .0001) or "very comfortable" (OR, 3.88; P < .0001) about discussing CAM, self-reported use of massage (OR, 2.20; P < .0001), and had formal CAM education (OR, 4.14; P = .0001) were more likely to ask about CAM use. Nurses who reported being "somewhat comfortable" (OR, 2.54; 95% confidence interval, 1.47-4.41; P = .0008) or "very comfortable" (OR, 7.46; P < .00001) and had formal CAM education (OR, 2.96; P < .0001) were also more likely to refer patients to CAM therapies.

CONCLUSIONS

Both patient and nurse characteristics were associated with discussions about CAM. Oncology institutions that prioritize evidence-based medicine should consider introducing CAM education to their nursing staff. Cancer 2016. © 2016 American Cancer Society.

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Caring for caregivers and patients: Research and clinical priorities for informal cancer caregiving

Informal/family caregivers are a fundamental source of care for cancer patients in the United States, yet the population of caregivers and their tasks, psychosocial needs, and health outcomes are not well understood. Changes in the nature of cancer care and its delivery, along with the growing population of survivors and their caregivers, warrant increased attention to the roles and demands of caregiving. This article reviews current evidence presented at a 2-day meeting examining the state of the science of informal cancer caregiving that was convened by the National Cancer Institute and the National Institute of Nursing Research. The meeting sought to define who is an informal cancer caregiver, summarize the state of the science in informal cancer caregiving, and describe both the kinds of interventions developed to address caregiving challenges and the various outcomes used to evaluate their impact. This article offers recommendations for moving science forward in 4 areas: 1) improving the estimation of the prevalence and burden of informal cancer caregiving; 2) advancing the development of interventions designed to improve outcomes for cancer patients, caregivers, and patient-caregiver dyads; 3) generating and testing strategies for integrating caregivers into formal health care settings; and 4) promoting the use of technology to support informal cancer caregivers. Cancer 2016. © 2016 American Cancer Society.

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Diagnostic and therapeutic update of mantle cell lymphoma (MCL): analysis of seven cases treated in a centre in one year

Carmen Herrero-Vicent, Isidro Machado, Carmen Illueca, Amparo Avaria, Claudia Salazar, Abraham Hernandez, Sergio Sandiego and Javier Lavernia

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Survival and clinical outcomes in patients with metastatic epidural spinal cord compression after spinal surgery: a prospective, multicenter, observational cohort study

High quality studies have been challenging to undertake in patients with metastatic epidural spinal cord compression. Nonetheless, in the article "Survival and Clinical Outcomes in Surgically Treated Patients ...

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Meeting report on the first Sino-Dutch symposium on oncology

On October 31, 2015, the first Sino-Dutch symposium on oncology was organized in Guangzhou (China). The symposium revealed similarities between Chinese and Dutch efforts to improve the care of tumor patients a...

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Prise en charge des sarcomes des tissus mous des membres par radiothérapie externe

Publication date: Available online 16 March 2016
Source:Cancer/Radiothérapie
Author(s): L. Moureau-Zabotto, M. Delannes, C. Le Péchoux, M.P. Sunyach, G. Kantor, P. Sargos, J. Thariat, C. Llacer-Moscardo
Les sarcomes des tissus mous sont des tumeurs rares. La chirurgie conservatrice suivie de radiothérapie postopératoire représente le standard de traitement dans la majorité des cas, la radiothérapie postopératoire améliorant le taux de contrôle local sans influencer la survie. Outre la qualité de l'exérèse chirurgicale qui reste le facteur pronostique majeur, l'importance du volume d'irradiation et en particulier des marges utilisées en radiothérapie externe se sont avérées influencer le contrôle local de la maladie. Dans cet article, nous proposons de réaliser une revue de la littérature, sur l'état actuel de nos connaissances sur ce sujet, sous la forme d'une controverse articulée de la sorte : pour ou contre des marges importantes en radiothérapie externe.Soft tissue sarcomas are rare tumours. Conservative surgery followed by postoperative radiation therapy represents the gold standard in the majority of cases. Postoperative radiotherapy improves local control without affecting survival. Besides the quality of surgical excision, which remains the major prognostic factor, the importance of the irradiation volume and particularly margins used in external beam radiotherapy were also found to influence local control of the disease. In this study, we propose to conduct a literature review on the present state of our knowledge on this subject in the form of an articulated controversy: in favour or opposed to large margins in external radiotherapy.



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Association de radiothérapie et d’hormonothérapie dans la prise en charge des cancers localisés de la prostate : où en est-on ?

Publication date: Available online 16 March 2016
Source:Cancer/Radiothérapie
Author(s): S. Bellefqih, K. Hadadi, I. Mezouri, A. Maghous, E. Marnouche, K. Andaloussi, M. Elmarjany, H. Sifat, H. Mansouri, N. Benjaafar




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Nitric Oxide and Reactive Oxygen Species: Clues to target Oxidative Damage Repair Defective Breast Cancers

Publication date: Available online 16 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Veena Somasundaram, Revathy Nadhan, K.H. Sreelatha, S.Satheesh Kumar, Priya Srinivas
The identification of various biomolecules in cancer progression and therapy has led to the exploration of the roles of two cardinal players, namely Nitric Oxide (NO) and Reactive Oxygen Species (ROS) in cancer. Both ROS and NO display bimodal fashions of functional activity in a concentration dependent manner, by inducing either pro- or anti- tumorigenic signals. Researchers have identified the potential capability of NO and ROS in therapies owing to their role in eliciting pro-apoptotic signals at higher concentrations and their ability to sensitize cancer cells to one another as well as to other therapeutics. We review the prospects of NO and ROS in cancer progression and therapy, and analyze the role of a combinatorial therapy wherein an NO donor (SNAP) is used to sensitize the oxidative damage repair defective, triple negative breast cancer cells (HCC 1937) to a potent ROS inducer. Preliminary findings support the potential to employ various combinatorial regimes for anti-cancer therapies with regard to exploiting the chemo-sensitization property of NO donors.



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Prognostic implications of securin expression and sub-cellular localization in human breast cancer

Abstract

Purpose

Securin belongs to a class of cell cycle regulators that prevent metaphase-to-anaphase transition until sister chromatid separation is complete. Evidence is accumulating that securin has a prognostic impact on a variety of malignancies but, thus far, the role and regulation of securin expression and its sub-cellular localization have not been systematically addressed in breast cancer.

Methods

In total 470 breast cancer specimens with follow-up data for up to 22 years were included. Immunohistochemical staining and immunofluorescence double-staining were performed for securin and its regulating proteins PTTG1IP, CDC20 and BUBR1. Prognostic associations were evaluated between the expression patterns of these proteins and established prognosticators of invasive breast cancer and patient survival.

Results

We found that a high fraction of securin expressing cancer cells predicted an unfavorable clinical outcome of the breast cancer patients (p < 0.001). Also in multivariate analyses, the fraction of securin expressing cancer cells served as an independent prognosticator of a poor survival (p < 0.0001). We also found that the sub-cellular localization of securin exhibited prognostic power, since cytoplasmic securin expression in the cancer cells appeared to be associated with aggressive breast cancer subtypes and high breast cancer-associated mortality rates (p = 0.003). Through immunofluorescence double-staining, we found that PTTG1IP, CDC20 and BUBR1 exhibited distinct patterns of co-expression with securin, suggesting a regulatory role in the metaphase-to-anaphase transition in human breast cancer cells. We also noted that a subgroup of triple-negative breast carcinomas exhibited deviant expression patterns for the proteins studied.

Conclusions

Our data indicate that securin expression may serve as a strong and independent prognosticator of breast cancer outcome and that a cytoplasmic localization of the protein may provide additional prognostic information, particularly in the biologically and clinically challenging subgroup of triple-negative breast carcinomas. The sub-cellular localization of securin appears to reflect the expression of PTTG1IP, CDC20 and BUBR1, which may participate in the regulation of securin activity and, ultimately, in the survival of breast cancer patients.

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Ganetespib radiosensitization for liver cancer therapy.

Related Articles

Ganetespib radiosensitization for liver cancer therapy.

Cancer Biol Ther. 2016 Mar 16;:0

Authors: Chettiar ST, Malek R, Annadanam A, Nugent KM, Kato Y, Wang H, Cades JA, Taparra K, Belcaid Z, Ballew M, Manmiller S, Proia D, Lim M, Anders RA, Herman JM, Tran PT

Abstract
Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on three liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33-1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies.

PMID: 26980196 [PubMed - as supplied by publisher]

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Ganetespib radiosensitization for liver cancer therapy.

Related Articles

Ganetespib radiosensitization for liver cancer therapy.

Cancer Biol Ther. 2016 Mar 16;:0

Authors: Chettiar ST, Malek R, Annadanam A, Nugent KM, Kato Y, Wang H, Cades JA, Taparra K, Belcaid Z, Ballew M, Manmiller S, Proia D, Lim M, Anders RA, Herman JM, Tran PT

Abstract
Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on three liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33-1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies.

PMID: 26980196 [PubMed - as supplied by publisher]

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Use of swabs for dry collection of self-samples to detect human papillomavirus among Malagasy women

Abstract

Background

Most women in developing countries have never attended cervical screening programmes and often little information exists on type-specific human papillomavirus (HPV) prevalence among these populations. Self-sampling for HPV testing (self-HPV) using a dry swab may be useful for establishing a screening program and evaluating HPV prevalence. Our aim was to evaluate self-HPV using a dry swab stored at room temperature.

Methods

This community-based study in Madagascar consisted of 449 women aged 30–65. Eligible women were provided a dry swab to perform self-HPV. HPV analysis was accomplished by two different real-time PCR tests using the same extracted DNA from the samples.

Results

Overall, 52 (11.6 %) specimens were invalid for HPV detection. The delay between sampling and laboratory processing of DNA extraction considerably increased invalid results. Overall HPV prevalence of 14 hrHPV types detected by the two PCR tests was found to be 38.2 % (n = 152). Distribution of 19 hrHPV and 9 low-risk HPV (lrHPV) types revealed most frequently 53 and 68 among hrHPV and HPV 54, HPV 70 and HPV 42 among lrHPV. Agreement between the two PCR methods for any of the 14 high-risk HPV (hrHPV) strains detected was 89.9 % (kappa = 0.77, 95 % CI: 0.71–0.84). In 385 (85.7 %) samples the DNA load of ß-globin demonstrated a signal with medium or high level copies. Conversely, in 28 (60.9 %) invalid samples the signal was undetectable. The HPV-DNA load signal was predominantly of intermediate level (58.5 %, n = 218).

Conclusions

Self-HPV using a dry swab stored at room temperature could be a useful method for HPV screening and for conducting population-based surveys on HPV prevalence in resource-poor settings.

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