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Cancers, Volume 9, Issue 2 (February 2017)

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Research

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Open AccessArticle Photodynamic Synergistic Effect of Pheophorbide a and Doxorubicin in Combined Treatment against Tumoral Cells
Cancers 2017, 9(2), 18; doi:10.3390/cancers9020018
Received: 8 November 2016 / Revised: 20 January 2017 / Accepted: 11 February 2017 / Published: 17 February 2017
Cited by 2 | PDF Full-text (10830 KB) | HTML Full-text | XML Full-text
Abstract
A combination of therapies to treat cancer malignancies is at the forefront of research with the aim to reduce drug doses (ultimately side effects) and diminish the possibility of resistance emergence given the multitarget strategy. With this goal in mind, in the present
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A combination of therapies to treat cancer malignancies is at the forefront of research with the aim to reduce drug doses (ultimately side effects) and diminish the possibility of resistance emergence given the multitarget strategy. With this goal in mind, in the present study, we report the combination between the chemotherapeutic drug doxorubicin (DOXO) and the photosensitizing agent pheophorbide a (PhA) to inactivate HeLa cells. Photophysical studies revealed that DOXO can quench the excited states of PhA, detracting from its photosensitizing ability. DOXO can itself photosensitize the production of singlet oxygen; however, this is largely suppressed when bound to DNA. Photodynamic treatments of cells incubated with DOXO and PhA led to different outcomes depending on the concentrations and administration protocols, ranging from antagonistic to synergic for the same concentrations. Taken together, the results indicate that an appropriate combination of DOXO with PhA and red light may produce improved cytotoxicity with a smaller dose of the chemotherapeutic drug, as a result of the different subcellular localization, targets and mode of action of the two agents. Full article
(This article belongs to the Special Issue Photodynamic Cancer Therapy)
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Review

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Open AccessReview Care at the Very End-of-Life: Dying Cancer Patients and Their Chosen Family’s Needs
Cancers 2017, 9(2), 11; doi:10.3390/cancers9020011
Received: 18 December 2016 / Revised: 16 January 2017 / Accepted: 18 January 2017 / Published: 24 January 2017
Cited by 3 | PDF Full-text (211 KB) | HTML Full-text | XML Full-text
Abstract
The majority of cancer deaths in countries such as Australia are predictable and most likely to occur in hospital. Despite this, hospitals remain challenged by providing the best care for this fragile cohort, often believing that care with palliative intent at the very
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The majority of cancer deaths in countries such as Australia are predictable and most likely to occur in hospital. Despite this, hospitals remain challenged by providing the best care for this fragile cohort, often believing that care with palliative intent at the very end-of-life is not the best approach to care. Given the importance that dying patients place on excellent symptom control, failing to provide good end-of-life care is likely to be contrary to the wishes of the imminently dying patient and their family. This becomes even more significant when the impact of care on the bereavement outcomes of families is considered. Given the rising numbers of predicable hospital deaths, an urgent need to address this exists, requiring health professionals to be cognisant of specific care domains already identified as significant for both patients and those closest to them in knowledge, care and affection. This non-systematic review’s aims are to summarise the symptoms most feared by people imminently facing death which is defined as the terminal phase of life, where death is imminent and likely to occur within hours to days, or very occasionally, weeks. Further, this paper will explore the incidence and management of problems that may affect the dying person which are most feared by their family. The final section of this work includes a brief discussion of the most significant issues that require attention. Full article
(This article belongs to the Special Issue End-of-Life Cancer Care)
Open AccessReview Interstitial Photodynamic Therapy—A Focused Review
Cancers 2017, 9(2), 12; doi:10.3390/cancers9020012
Received: 1 December 2016 / Revised: 13 January 2017 / Accepted: 20 January 2017 / Published: 24 January 2017
Cited by 6 | PDF Full-text (671 KB) | HTML Full-text | XML Full-text
Abstract
Multiple clinical studies have shown that interstitial photodynamic therapy (I-PDT) is a promising modality in the treatment of locally-advanced cancerous tumors. However, the utilization of I-PDT has been limited to several centers. The objective of this focused review is to highlight the different
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Multiple clinical studies have shown that interstitial photodynamic therapy (I-PDT) is a promising modality in the treatment of locally-advanced cancerous tumors. However, the utilization of I-PDT has been limited to several centers. The objective of this focused review is to highlight the different approaches employed to administer I-PDT with photosensitizers that are either approved or in clinical studies for the treatment of prostate cancer, pancreatic cancer, head and neck cancer, and brain cancer. Our review suggests that I-PDT is a promising treatment in patients with large-volume or thick tumors. Image-based treatment planning and real-time dosimetry are required to optimize and further advance the utilization of I-PDT. In addition, pre- and post-imaging using computed tomography (CT) with contrast may be utilized to assess the response. Full article
(This article belongs to the Special Issue Photodynamic Cancer Therapy)
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Open AccessReview Immune Modulation by Androgen Deprivation and Radiation Therapy: Implications for Prostate Cancer Immunotherapy
Cancers 2017, 9(2), 13; doi:10.3390/cancers9020013
Received: 3 December 2016 / Accepted: 20 January 2017 / Published: 27 January 2017
Cited by 3 | PDF Full-text (846 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer patients often receive androgen deprivation therapy (ADT) in combination with radiation therapy (RT). Recent evidence suggests that both ADT and RT have immune modulatory properties. First, ADT can cause infiltration of lymphocytes into the prostate, although it remains unclear whether the
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Prostate cancer patients often receive androgen deprivation therapy (ADT) in combination with radiation therapy (RT). Recent evidence suggests that both ADT and RT have immune modulatory properties. First, ADT can cause infiltration of lymphocytes into the prostate, although it remains unclear whether the influx of lymphocytes is beneficial, particularly with the advent of new classes of androgen blockers. Second, in rare cases, radiation can elicit immune responses that mediate regression of metastatic lesions lying outside the field of radiation, a phenomenon known as the abscopal response. In light of these findings, there is emerging interest in exploiting any potential synergy between ADT, RT, and immunotherapy. Here, we provide a comprehensive review of the rationale behind combining immunotherapy with ADT and RT for the treatment of prostate cancer, including an examination of the current clinical trials that employ this combination. The reported outcomes of several trials demonstrate the promise of this combination strategy; however, further scrutiny is needed to elucidate how these standard therapies interact with immune modulators. In addition, we discuss the importance of synchronizing immune modulation relative to ADT and RT, and provide insight into elements that may impact the ability to achieve maximum synergy between these treatments. Full article
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Open AccessReview A Tale of Two Signals: AR and WNT in Development and Tumorigenesis of Prostate and Mammary Gland
Cancers 2017, 9(2), 14; doi:10.3390/cancers9020014
Received: 6 December 2016 / Revised: 19 January 2017 / Accepted: 24 January 2017 / Published: 27 January 2017
Cited by 1 | PDF Full-text (2049 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer (PCa) is one of the most common cancers and among the leading causes of cancer deaths for men in industrialized countries. It has long been recognized that the prostate is an androgen-dependent organ and PCa is an androgen-dependent disease. Androgen action
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Prostate cancer (PCa) is one of the most common cancers and among the leading causes of cancer deaths for men in industrialized countries. It has long been recognized that the prostate is an androgen-dependent organ and PCa is an androgen-dependent disease. Androgen action is mediated by the androgen receptor (AR). Androgen deprivation therapy (ADT) is the standard treatment for metastatic PCa. However, almost all advanced PCa cases progress to castration-resistant prostate cancer (CRPC) after a period of ADT. A variety of mechanisms of progression from androgen-dependent PCa to CRPC under ADT have been postulated, but it remains largely unclear as to when and how castration resistance arises within prostate tumors. In addition, AR signaling may be modulated by extracellular factors among which are the cysteine-rich glycoproteins WNTs. The WNTs are capable of signaling through several pathways, the best-characterized being the canonical WNT/β-catenin/TCF-mediated canonical pathway. Recent studies from sequencing PCa genomes revealed that CRPC cells frequently harbor mutations in major components of the WNT/β-catenin pathway. Moreover, the finding of an interaction between β-catenin and AR suggests a possible mechanism of cross talk between WNT and androgen/AR signaling pathways. In this review, we discuss the current knowledge of both AR and WNT pathways in prostate development and tumorigenesis, and their interaction during development of CRPC. We also review the possible therapeutic application of drugs that target both AR and WNT/β-catenin pathways. Finally, we extend our review of AR and WNT signaling to the mammary gland system and breast cancer. We highlight that the role of AR signaling and its interaction with WNT signaling in these two hormone-related cancer types are highly context-dependent. Full article
(This article belongs to the Special Issue AR Signaling in Human Malignancies: Prostate Cancer and Beyond)
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Open AccessReview Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions
Cancers 2017, 9(2), 15; doi:10.3390/cancers9020015
Received: 14 December 2016 / Accepted: 18 January 2017 / Published: 27 January 2017
Cited by 3 | PDF Full-text (561 KB) | HTML Full-text | XML Full-text
Abstract
Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were
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Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA) approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for firstline platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC. Full article
(This article belongs to the Special Issue Cancer Immunotherapies)
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Open AccessReview Epidermal Growth Factor Pathway Signaling in Drosophila Embryogenesis: Tools for Understanding Cancer
Cancers 2017, 9(2), 16; doi:10.3390/cancers9020016
Received: 14 December 2016 / Revised: 2 February 2017 / Accepted: 3 February 2017 / Published: 7 February 2017
Cited by 2 | PDF Full-text (917 KB) | HTML Full-text | XML Full-text
Abstract
EGF signaling is a well-known oncogenic pathway in animals. It is also a key developmental pathway regulating terminal and dorsal-ventral patterning along with many other aspects of embryogenesis. In this review, we focus on the diverse roles for the EGF pathway in Drosophila
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EGF signaling is a well-known oncogenic pathway in animals. It is also a key developmental pathway regulating terminal and dorsal-ventral patterning along with many other aspects of embryogenesis. In this review, we focus on the diverse roles for the EGF pathway in Drosophila embryogenesis. We review the existing body of evidence concerning EGF signaling in Drosophila embryogenesis focusing on current uncertainties in the field and areas for future study. This review provides a foundation for utilizing the Drosophila model system for research into EGF effects on cancer. Full article
(This article belongs to the Special Issue EGFR Family Signaling in Cancer)
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Open AccessReview Androgen Receptor Signaling in Salivary Gland Cancer
Cancers 2017, 9(2), 17; doi:10.3390/cancers9020017
Received: 22 December 2016 / Revised: 28 January 2017 / Accepted: 3 February 2017 / Published: 8 February 2017
Cited by 1 | PDF Full-text (348 KB) | HTML Full-text | XML Full-text
Abstract
Salivary gland cancers comprise a small subset of human malignancies, and are classified into multiple subtypes that exhibit diverse histology, molecular biology and clinical presentation. Local disease is potentially curable with surgery, which may be combined with adjuvant radiotherapy. However, metastatic or unresectable
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Salivary gland cancers comprise a small subset of human malignancies, and are classified into multiple subtypes that exhibit diverse histology, molecular biology and clinical presentation. Local disease is potentially curable with surgery, which may be combined with adjuvant radiotherapy. However, metastatic or unresectable tumors rarely respond to chemotherapy and carry a poorer prognosis. Recent molecular studies have shown evidence of androgen receptor signaling in several types of salivary gland cancer, mainly salivary duct carcinoma. Successful treatment with anti-androgen therapy in other androgen receptor-positive malignancies such as prostate and breast cancer has inspired researchers to investigate this treatment in salivary gland cancer as well. In this review, we describe the prevalence, biology, and therapeutic implications of androgen receptor signaling in salivary gland cancer. Full article
(This article belongs to the Special Issue AR Signaling in Human Malignancies: Prostate Cancer and Beyond)
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Open AccessReview Oncologic Photodynamic Therapy: Basic Principles, Current Clinical Status and Future Directions
Cancers 2017, 9(2), 19; doi:10.3390/cancers9020019
Received: 16 December 2016 / Revised: 10 February 2017 / Accepted: 12 February 2017 / Published: 18 February 2017
Cited by 14 | PDF Full-text (670 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells
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Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells and/or vasculature, and induce inflammatory and immune responses. PDT is a two-stage procedure, which starts with photosensitizer administration followed by a locally directed light exposure, with the aim of confined tumor destruction. Since its regulatory approval, over 30 years ago, PDT has been the subject of numerous studies and has proven to be an effective form of cancer therapy. This review provides an overview of the clinical trials conducted over the last 10 years, illustrating how PDT is applied in the clinic today. Furthermore, examples from ongoing clinical trials and the most recent preclinical studies are presented, to show the directions, in which PDT is headed, in the near and distant future. Despite the clinical success reported, PDT is still currently underutilized in the clinic. We also discuss the factors that hamper the exploration of this effective therapy and what should be changed to render it a more effective and more widely available option for patients. Full article
(This article belongs to the Special Issue Photodynamic Cancer Therapy)
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Open AccessReview Androgen Receptor Signaling in Bladder Cancer
Cancers 2017, 9(2), 20; doi:10.3390/cancers9020020
Received: 1 December 2016 / Revised: 24 January 2017 / Accepted: 16 February 2017 / Published: 22 February 2017
PDF Full-text (483 KB) | HTML Full-text | XML Full-text
Abstract
Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific
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Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer. Full article
(This article belongs to the Special Issue AR Signaling in Human Malignancies: Prostate Cancer and Beyond)
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