The establishment of an ISO compliant cancer biobank for Jordan and its neighboring countries through knowledge transfer and training

Research studies aimed at advancing cancer prevention, diagnosis, and treatment depend on a number of key resources, including a ready supply of high-quality annotated biospecimens from diverse ethnic populations that can be used to test new drugs, assess the validity of prognostic biomarkers, and develop tailor-made therapies. In November 2011, KHCCBIO was established at the King Hussein Cancer Center (KHCC) with the support of Seventh Framework Programme (FP7) funding from the European Union (khccbio.khcc.jo). KHCCBIO was developed for the purpose of achieving an ISO accredited cancer biobank through the collection, processing, and preservation of high-quality, clinically annotated biospecimens from consenting cancer patients, making it the first cancer biobank of its kind in Jordan. The establishment of a state-of-the-art, standardized biospecimen repository of matched normal and lung tumor tissue, in addition to blood components such as serum, plasma, and white blood cells, was achieved through the support and experience of its European partners, Trinity College Dublin, Biostor Ireland, and accelopment AG. To date, KHCCBIO along with its partners, have worked closely in establishing an ISO Quality Management System (QMS) under which the biobank will operate. A Quality Policy Manual, Validation, and Training plan have been developed in addition to the development of standard operating procedures (SOPs) for consenting policies on ethical issues, data privacy, confidentiality, and biobanking bylaws. SOPs have also been drafted according to best international practices and implemented for the donation, procurement, processing, testing, preservation, storage, and distribution of tissues and blood samples from lung cancer patients, which will form the basis for the procurement of other cancer types. KHCCBIO will be the first ISO accredited cancer biobank from a diverse ethnic Middle Eastern and North African population. It will provide a unique and valuable resource of high-quality human biospecimens and anonymized clinicopathological data to the cancer research communities world-wide.

Differential effects of tissue culture coating substrates on prostate cancer cell adherence, morphology and behavior

Weak cell-surface adhesion of cell lines to tissue culture surfaces is a common problem and presents technical limitations to the design of experiments. To overcome this problem, various surface coating protocols have been developed. However, a comparative and precise real-time measurement of their impact on cell behavior has not been conducted. The prostate cancer cell line LNCaP, derived from a patient lymph node metastasis, is a commonly used model system in prostate cancer research. However, the cells’ characteristically weak attachment to the surface of tissue culture vessels and cover slips has impeded their manipulation and analysis and use in high throughput screening. To improve the adherence of LNCaP cells to the culture surface, we compared different coating reagents (poly-L-lysine, poly-L-ornithine, collagen type IV, fibronectin, and laminin) and culturing conditions and analyzed their impact on cell proliferation, adhesion, morphology, mobility and gene expression using real-time technologies. The results showed that fibronectin, poly-L-lysine and poly-L-ornithine improved LNCaP cells adherence and provoked cell morphology alterations, such as increase of nuclear and cellular area. These coating reagents also induced a higher expression of F-actin and reduced cell mobility. In contrast, laminin and collagen type IV did not improve adherence but promoted cell aggregation and affected cell morphology. Cells cultured in the presence of laminin displayed higher mobility than control cells. All the coating conditions significantly affected cell viability; however, they did not affect the expression of androgen receptor-regulated genes. Our comparative findings provide important insight for the selection of the ideal coating reagent and culture conditions for the cancer cell lines with respect to their effect on proliferation rate, attachment, morphology, migration, transcriptional response and cellular cytoskeleton arrangement.

An individual-based versus group-based exercise and counselling intervention for improving quality of life in breast cancer survivors. A feasibility and efficacy study

Background Cancer and its treatments produce lingering side-effects that undermine the quality of life (QOL) of survivors. Exercise and psycho-therapies increase QOL among survivors, however, research is needed to identify intervention characteristics most associated with such improvements. Objective This research aimed to assess the feasibility of a 9 week individual or group based exercise and counselling program, and to examine if a group based intervention is as effective at improving the QOL of breast cancer survivors as an individual-based intervention. Methods A three group design was implemented to compare the efficacy of a 9 week individual (IEC n = 12) and group based exercise and counselling (GEC n = 14) intervention to a usual care (UsC n = 10) group on QOL of thirty-six breast cancer survivors. Results Across all groups, 90% of participants completed the interventions, with no adverse effects documented. At the completion of the intervention, there was a significant difference between groups for change in global QOL across time (p < 0.023), with IEC improving significantly more (15.0 points) than the UsC group (1.8 points). The effect size was moderate (0.70). Although the GEC improved QOL by almost 10.0 points, this increase did not reach significance. Both increases were above the minimally important difference of 7–8 points. Conclusion These preliminary results suggest a combined exercise and psychological counseling program is both a feasible and acceptable intervention for breast cancer survivors. Whilst both the individual and group interventions improved QOL above the clinically important difference, only the individual based intervention was significant when compared to UsC.

Improving muscular endurance with the MVe Fitness ChairTM in breast cancer survivors: A feasibility and efficacy study

Objectives To assess the feasibility and efficacy of delivering Pilates exercises for resistance training to breast cancer survivors using the MVe Fitness Chair™. Design Pilot randomized controlled trial. Methods Twenty-six female breast cancer survivors were randomized to use the MVe Fitness Chair™ (n = 8), traditional resistance training (n = 8), or a control group (no exercise) (CO) (n = 10). The MVe Fitness Chair™ and traditional resistance training groups completed 8 weeks of exercise. Muscular endurance was assessed pre and post-test for comparisons within and between groups using push ups, curl ups, and the Dynamic Muscular Endurance Test Battery for Cancer Patients of Various Ages. Results Feasibility of the MVe Fitness Chair™ was good, evidenced by over 80% adherence for both exercise groups and positive narrative feedback. Significant improvements in muscular endurance were observed in the MVe Fitness Chair™ (p < 0.002) and traditional resistance training groups (p < 0.001), but there were no differences in improvement between the MVe Fitness Chair™ and traditional resistance training groups (p < 0.711) indicating that Pilates and traditional resistance training may be equally effective at improving muscular endurance in this population. Conclusions The MVe Fitness Chair™ is feasible for use in breast cancer survivors. It appears to promote similar improvements in muscular endurance when compared to traditional resistance training, but has several advantages over traditional resistance training, including cost, logistics, enjoyment, and ease of learning.

The origins and radiation of Australian Coptotermes termites: From rainforest to desert dwellers

The termite genus Coptotermes (Rhinotermitidae) is found in Asia, Africa, Central/South America and Australia, with greatest diversity in Asia. Some Coptotermes species are amongst the world’s most damaging invasive termites, but the genus is also significant for containing the most sophisticated mound-building termites outside the family Termitidae. These mound-building Coptotermes occur only in Australia. Despite its economic and evolutionary significance, the biogeographic history of the genus has not been well investigated, nor has the evolution of the Australian mound-building species. We present here the first phylogeny of the Australian Coptotermes to include representatives from all described species. We combined our new data with previously generated data to estimate the first phylogeny to include representatives from all continents where the genus is found. We also present the first estimation of divergence dates during the evolution of the genus. We found the Australian Coptotermes to be monophyletic and most closely related to the Asian Coptotermes, with considerable genetic diversity in some Australian taxa possibly representing undescribed species. The Australian mound-building species did not form a monophyletic clade. Our ancestral state reconstruction analysis indicated that the ancestral Australian Coptotermes was likely to have been a tree nester, and that mound-building behaviour has arisen multiple times. The Australian Coptotermes were found to have diversified ∼13 million years ago, which plausibly matches with the narrowing of the Arafura Sea allowing Asian taxa to cross into Australia. The first diverging Coptotermes group was found to be African, casting doubt on the previously raised hypothesis that the genus has an Asian origin.

Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1

Obesity and metabolic syndrome are associated with several cancers, however, the molecular mechanisms remain to be fully elucidated. Recent studies suggest that hypercholesterolemia increases intratumoral androgen signaling in prostate cancer, but it is unclear whether androgenindependent mechanisms also exist. Since hypercholesterolemia is associated with advanced, castrate-resistant prostate cancer, in this study, we aimed to determine whether and how hypercholesterolemia affects prostate cancer progression in the absence of androgen signaling. We demonstrate that diet-induced hypercholesterolemia promotes orthotopic xenograft PC-3 cell metastasis, concomitant with elevated expression of caveolin-1 and IQGAP1 in xenograft tumor tissues. In vitro cholesterol treatment of PC-3 cells stimulated migration and increased IQGAP1 and caveolin-1 protein level and localization to a detergent-resistant fraction. Down-regulation of caveolin-1 or IQGAP1 in PC-3 cells reduced migration and invasion in vitro, and hypercholesterolemia-induced metastasis in vivo. Double knock-down of caveolin-1 and IQGAP1 showed no additive effect, suggesting that caveolin-1 and IQGAP1 act via the same pathway. Taken together, our data show that hypercholesterolemia promotes prostate cancer metastasis independent of the androgen pathway, in part by increasing IQGAP1 and caveolin-1. These results have broader implications for managing metastasis of cancers in general as IQGAP1 and hypercholesterolemia are implicated in the progression of several cancers.

The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

Investigation of fiducial marker and soft-tissue image guidance techniques in prostate radiation therapy

This thesis examines and compares imaging methods used during the radiotherapy treatment of prostate cancer. The studies found that radiation therapists were able to localise and target the prostate consistently with planar imaging techniques and that the use of small gold markers in the prostate reduced the variation in prostate localisation when using volumetric imaging. It was concluded that larger safety margins are required when using volumetric imaging without gold markers.

Effects and feasibility of a multi-disciplinary orientation program for newly registered cancer patients : design of a randomised controlled trial

Background Diagnosis and treatment of cancer can contribute to psychological distress and anxiety amongst patients. Evidence indicates that information giving can be beneficial in reducing patient anxiety, so oncology specific information may have a major impact on this patient group. This study investigates the effects of an orientation program on levels of anxiety and self-efficacy amongst newly registered cancer patients who are about to undergo chemotherapy and/or radiation therapy in the cancer care centre of a large tertiary Australian hospital. Methods The concept of interventions for orienting new cancer patients needs revisiting due to the dynamic health care system. Historically, most orientation programs at this cancer centre were conducted by one nurse. A randomised controlled trial has been designed to test the effectiveness of an orientation program with bundled interventions; a face-to-face program which includes introduction to the hospital facilities, introduction to the multi-disciplinary team and an overview of treatment side effects and self care strategies. The aim is to orientate patients to the cancer centre and to meet the health care team. We hypothesize that patients who receive this orientation will experience lower levels of anxiety and distress, and a higher level of self-efficacy. Discussion An orientation program is a common health care service provided by cancer care centres for new cancer patients. Such programs aim to give information to patients at the beginning of their encounter at a cancer care centre. It is clear in the literature that interventions that aim to improve self-efficacy in patients may demonstrate potential improvement in health outcomes. Yet, evidence on the effects of orientation programs for cancer patients on self-efficacy remains scarce, particularly with respect to the use of multidisciplinary team members. This paper presents the design of a randomised controlled trial that will evaluate the effects and feasibility of a multidisciplinary orientation program for new cancer patients.

Safety, feasibility and effects of an individualised walking intervention for women undergoing chemotherapy for ovarian cancer : a pilot study

Background: Exercise interventions during adjuvant cancer therapy have been shown to increase functional capacity, relieve fatigue and distress and may assist rates of chemotherapy completion. These studies have been limited to breast, gastric and mixed cancer groups and it is not yet known if a similar intervention is even feasible among women with ovarian cancer. We aimed to assess safety, feasibility and potential effect of a walking intervention in women undergoing chemotherapy for ovarian cancer. Methods: Women newly diagnosed with ovarian cancer were recruited to participate in an individualised walking intervention throughout chemotherapy and were assessed pre-and post-intervention. Feasibility measures included session adherence, compliance with exercise physiologist prescribed walking targets and self-reported program acceptability. Changes in objective physical functioning (6 minute walk test), self-reported distress (Hospital Anxiety and Depression Scale), symptoms (Memorial Symptom Assessment Scale - Physical) and quality of life (Functional Assessment of Cancer Therapy - Ovarian) were calculated, and chemotherapy completion and adverse intervention effects recorded. Results: Seventeen women were enrolled (63% recruitment rate). Mean age was 60 years (SD = 8 years), 88% were diagnosed with FIGO stage III or IV disease, 14 women underwent adjuvant and three neo-adjuvant chemotherapy. On average, women adhered to > 80% of their intervention sessions and complied with 76% of their walking targets, with the majority walking four days a week at moderate intensity for 30 minutes per session. Meaningful improvements were found in physical functioning, physical symptoms, physical well-being and ovarian cancerspecific quality of life. Most women (76%) completed ≥85% of their planned chemotherapy dose. There were no withdrawals or serious adverse events and all women reported the program as being helpful. Conclusions: These positive preliminary results suggest that this walking intervention for women receiving chemotherapy for ovarian cancer is safe, feasible and acceptable and could be used in development of future work. Trial registration: ACTRN12609000252213

Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer : potential targets for chemoprevention and systemic therapy

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from growth and proliferation to cell death. Cyclooxygenase (COX)-2 is an enzyme which catalyses the conversion of arachidonic acid to prostagladins and thromboxane. It is induced by various inflammatory stimuli, including the pro-inflammatory cytokines, Interleukin (IL)-1β, Tumour Necrosis Factor (TNF)-α and IL-2. Both EGFR and COX-2 are over-expressed in non-small cell lung cancer (NSCLC) and have been implicated in the early stages of tumourigenesis. This paper considers their roles in the development and progression of lung cancer, their potential interactions, and reviews the recent progress in cancer therapies that are directed toward these targets. An increasing body of evidence suggests that selective inhibitors of both EGFR and COX-2 are potential therapeutic agents for the treatment of NSCLC, in the adjuvant, metastatic and chemopreventative settings. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Reversibility of liver failure secondary to metastatic breast cancer by vinorelbine and cisplatin chemotherapy

Purpose: The development of liver metastases from breast cancer is associated with a very poor prognosis, estimated at 4 months median survival. Since treatment with many chemotherapeutic agents is relatively contraindicated, we assessed the safety, tolerability and potential efficacy of combination chemotherapy with vinorelbine and cisplatin (ViP). Method: Pilot study in 11 patients with histologically confirmed breast carcinoma, radiological evidence of liver metastases and serum bilirubin greater than 1.5 times the upper limit of normal. Patients received up to six cycles of cisplatin (75 mg/m 2) every 21 days and vinorelbine (20 mg/m 2) on days 1 and 8 of every 21-day cycle. Measurement of liver lesions was performed on CT scan every 8 weeks into treatment. Results: The most frequently reported adverse event was myelosuppression. Other adverse effects included nausea, vomiting and mild neurotoxicity. Two patients died after one treatment with ViP, one of whom suffered an intracerebral haemorrhage that was possibly treatment-related. Improvement in liver function tests was observed in 10 patients, and mean time to normalization of bilirubin levels was 36 days. Partial responses were documented radiologically in 7 out of 11 patients treated. Median overall survival from trial entry was 6.5 months (range 11-364 days), with one patient alive 13 months from trial entry. Conclusion: Normalization of liver function is possible with ViP treatment of metastatic breast cancer, offering the potential to prolong survival. Phase II clinical trials of this regimen in this patient group should include measurement of quality of life in order to assess risk versus benefit.

Assessment of cone beam CT registration for prostate radiation therapy : fiducial marker and soft tissue methods

Introduction This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM) and the soft tissue prostate (CBCTST). Methods Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland–Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST. Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM. Results CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of −4.9 to 2.6, −1.6 to 2.5 and −4.7 to 1.9 mm in the superior–inferior, left–right and anterior–posterior planes, respectively. Conclusions Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.