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Cancers, Volume 8, Issue 11 (November 2016) – 7 articles

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560 KiB  
Article
Caregiving and Its Resulting Effects—The Care Study to Evaluate the Effects of Caregiving on Caregivers of Patients with Advanced Cancer in Singapore
by Cheryl Kai Ting Chua, Jun Tian Wu, Yin Yee Wong, Limin Qu, Yung Ying Tan, Patricia Soek Hui Neo and Grace Suyin Pang
Cancers 2016, 8(11), 105; https://doi.org/10.3390/cancers8110105 - 15 Nov 2016
Cited by 22 | Viewed by 6246
Abstract
Informal caregivers (IC) are key to enabling home deaths, where preferred, at the end-of-life. Significant morbidity from advanced cancer can make caregiving burdensome. However, knowledge about the nature of the caregiving burden for caregivers in Singapore is limited. Hence, the key objective in [...] Read more.
Informal caregivers (IC) are key to enabling home deaths, where preferred, at the end-of-life. Significant morbidity from advanced cancer can make caregiving burdensome. However, knowledge about the nature of the caregiving burden for caregivers in Singapore is limited. Hence, the key objective in this study was to examine the impact of the caregiving burden on quality of life (QOL), mental health and work capacity among local ICs. Eligible English-speaking ICs of hospitalized advanced cancer patients were recruited through non-random sampling. The Zarit Burden Interview (ZBI), Caregiver Quality of Life Index—Cancer (CQOLC), Center for Epidemiologic Studies Depression Scale—Revised (CESD-R), and Work Productivity and Activity Impairment Questionnaire (WPAI) were interviewer-administered to eligible ICs. Altogether, 16 ICs were surveyed. The mean age of ICs was 43.8 years. Most were children of patients (43.8%), and eight ICs had high burden (ZBI > 17). Those with ZBI > 17 had lower QOL, higher depression scores as well as greater work and activity impairment. In conclusion, high caregiver burden has adverse effects on QOL, mental health and work productivity. Non-physical elements of caregiving (particularly financial and decision-making) and increased number of care roles undertaken by a single IC contribute to high burden. Future interventions for caregiving burden in Singapore should also address the financial and decision-making aspects of caregiving. Outsourcing selected aspects of the caregiving role to community services may reduce the number of caregiving aspects undertaken by a single IC and caregiver burden. Full article
(This article belongs to the Special Issue End-of-Life Cancer Care)
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149 KiB  
Commentary
A Music Therapist Shares Stories of Patients with Cancer
by Kathy Jo Gutgsell
Cancers 2016, 8(11), 104; https://doi.org/10.3390/cancers8110104 - 15 Nov 2016
Cited by 48 | Viewed by 3750
Abstract
Since the publication of my research reporting that music therapy reduces pain in palliative care patients [1], many people have expressed curiosity about what it is I do with patients.[...] Full article
(This article belongs to the Special Issue End-of-Life Cancer Care)
1309 KiB  
Review
The Receptor Tyrosine Kinase AXL in Cancer Progression
by Erinn B. Rankin and Amato J. Giaccia
Cancers 2016, 8(11), 103; https://doi.org/10.3390/cancers8110103 - 09 Nov 2016
Cited by 115 | Viewed by 13483
Abstract
The AXL receptor tyrosine kinase (AXL) has emerged as a promising therapeutic target for cancer therapy. Recent studies have revealed a central role of AXL signaling in tumor proliferation, survival, stem cell phenotype, metastasis, and resistance to cancer therapy. Moreover, AXL is expressed [...] Read more.
The AXL receptor tyrosine kinase (AXL) has emerged as a promising therapeutic target for cancer therapy. Recent studies have revealed a central role of AXL signaling in tumor proliferation, survival, stem cell phenotype, metastasis, and resistance to cancer therapy. Moreover, AXL is expressed within cellular components of the tumor microenvironment where AXL signaling contributes to the immunosuppressive and protumorigenic phenotypes. A variety of AXL inhibitors have been developed and are efficacious in preclinical studies. These agents offer new opportunities for therapeutic intervention in the prevention and treatment of advanced disease. Here we review the literature that has illuminated the cellular and molecular mechanisms by which AXL signaling promotes tumor progression and we will discuss the therapeutic potential of AXL inhibition for cancer therapy. Full article
(This article belongs to the Special Issue TAM family receptors in cancer biology and therapeutic resistance)
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204 KiB  
Review
Advance Care Planning in Glioblastoma Patients
by Lara Fritz, Linda Dirven, Jaap C. Reijneveld, Johan A. F. Koekkoek, Anne M. Stiggelbout, H. Roeline W. Pasman and Martin J. B. Taphoorn
Cancers 2016, 8(11), 102; https://doi.org/10.3390/cancers8110102 - 08 Nov 2016
Cited by 45 | Viewed by 7410
Abstract
Despite multimodal treatment with surgery, radiotherapy and chemotherapy, glioblastoma is an incurable disease with a poor prognosis. During the disease course, glioblastoma patients may experience progressive neurological deficits, symptoms of increased intracranial pressure such as drowsiness and headache, incontinence, seizures and progressive cognitive [...] Read more.
Despite multimodal treatment with surgery, radiotherapy and chemotherapy, glioblastoma is an incurable disease with a poor prognosis. During the disease course, glioblastoma patients may experience progressive neurological deficits, symptoms of increased intracranial pressure such as drowsiness and headache, incontinence, seizures and progressive cognitive dysfunction. These patients not only have cancer, but also a progressive brain disease. This may seriously interfere with their ability to make their own decisions regarding treatment. It is therefore warranted to involve glioblastoma patients early in the disease trajectory in treatment decision-making on their future care, including the end of life (EOL) care, which can be achieved with Advance Care Planning (ACP). Although ACP, by definition, aims at timely involvement of patients and proxies in decision-making on future care, the optimal moment to initiate ACP discussions in the disease trajectory of glioblastoma patients remains controversial. Moreover, the disease-specific content of these ACP discussions needs to be established. In this article, we will first describe the history of patient participation in treatment decision-making, including the shift towards ACP. Secondly, we will describe the possible role of ACP for glioblastoma patients, with the specific aim of treatment of disease-specific symptoms such as somnolence and dysphagia, epileptic seizures, headache, and personality changes, agitation and delirium in the EOL phase, and the importance of timing of ACP discussions in this patient population. Full article
(This article belongs to the Special Issue End-of-Life Cancer Care)
1060 KiB  
Review
Targeting the TAM Receptors in Leukemia
by Madeline G. Huey, Katherine A. Minson, H. Shelton Earp, Deborah DeRyckere and Douglas K. Graham
Cancers 2016, 8(11), 101; https://doi.org/10.3390/cancers8110101 - 08 Nov 2016
Cited by 30 | Viewed by 10810
Abstract
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell [...] Read more.
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition. Full article
(This article belongs to the Special Issue TAM family receptors in cancer biology and therapeutic resistance)
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3614 KiB  
Article
TβRIII Expression in Human Breast Cancer Stroma and the Role of Soluble TβRIII in Breast Cancer Associated Fibroblasts
by Bojana Jovanović, Michael W. Pickup, Anna Chytil, Agnieszka E. Gorska, Kimberly C. Johnson, Harold L. Moses and Philip Owens
Cancers 2016, 8(11), 100; https://doi.org/10.3390/cancers8110100 - 04 Nov 2016
Cited by 9 | Viewed by 5705
Abstract
The TGF-β pathway plays a major role in tumor progression through regulation of epithelial and stromal cell signaling. Dysfunction of the pathway can lead to carcinoma progression and metastasis. To gain insight into the stromal role of the TGF-β pathway in breast cancer, [...] Read more.
The TGF-β pathway plays a major role in tumor progression through regulation of epithelial and stromal cell signaling. Dysfunction of the pathway can lead to carcinoma progression and metastasis. To gain insight into the stromal role of the TGF-β pathway in breast cancer, we performed laser capture microdissection (LCM) from breast cancer patients and reduction mammoplasty patients. Microdissected tumor stroma and normal breast stroma were examined for gene expression. Expression of the TGF-β type III receptor (TGFBR3) was greatly decreased in the tumor stroma compared to control healthy breast tissue. These results demonstrated a 44-fold decrease in TGFBR3 mRNA in tumor stroma in comparison to control tissue. We investigated publicly available databases, and have identified that TGFBR3 mRNA levels are decreased in tumor stroma. We next investigated fibroblast cell lines derived from cancerous and normal breast tissue and found that in addition to mRNA levels, TβRIII protein levels were significantly reduced. Having previously identified that cancer-associated fibroblasts secrete greater levels of tumor promoting cytokines, we investigated the consequences of soluble-TβRIII (sTβRIII) on fibroblasts. Fibroblast conditioned medium was analyzed for 102 human secreted cytokines and distinct changes in response to sTβRIII were observed. Next, we used the fibroblast-conditioned medium to stimulate human monocyte cell line THP-1. These results indicate a distinct transcriptional response depending on sTβRIII treatment and whether it was derived from normal or cancerous breast tissue. We conclude that the effect of TβRIII has distinct roles not only in cancer-associated fibroblasts but that sTβRIII has distinct paracrine functions in the tumor microenvironment. Full article
(This article belongs to the Special Issue Cancer-Associated Fibroblasts)
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1570 KiB  
Review
Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors
by Victor M. Bii and Grant D. Trobridge
Cancers 2016, 8(11), 99; https://doi.org/10.3390/cancers8110099 - 25 Oct 2016
Cited by 3 | Viewed by 5933
Abstract
Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a [...] Read more.
Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types. Full article
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