Biomedicines

16 pages, 1742 KiB

Open AccessReview

The Direct and Indirect Roles of NF-κB in Cancer: Lessons from Oncogenic Fusion Proteins and Knock-in Mice

by Tabea Riedlinger, Jana Haas, Julia Busch, Bart Van de Sluis, Michael Kracht and M. Lienhard Schmitz

Biomedicines 2018, 6(1), 36; https://doi.org/10.3390/biomedicines6010036 - 19 Mar 2018

Cited by 18 | Viewed by 5683 | Correction

Abstract

NF-κB signaling pathways play an important role in the regulation of cellular immune and stress responses. Aberrant NF-κB activity has been implicated in almost all the steps of cancer development and many of the direct and indirect contributions of this transcription factor system [...] Read more.

NF-κB signaling pathways play an important role in the regulation of cellular immune and stress responses. Aberrant NF-κB activity has been implicated in almost all the steps of cancer development and many of the direct and indirect contributions of this transcription factor system for oncogenesis were revealed in the recent years. The indirect contributions affect almost all hallmarks and enabling characteristics of cancer, but NF-κB can either promote or antagonize these tumor-supportive functions, thus prohibiting global NF-κB inhibition. The direct effects are due to mutations of members of the NF-κB system itself. These mutations typically occur in upstream components that lead to the activation of NF-κB together with further oncogenesis-promoting signaling pathways. In contrast, mutations of the downstream components, such as the DNA-binding subunits, contribute to oncogenic transformation by affecting NF-κB-driven transcriptional output programs. Here, we discuss the features of recently identified oncogenic RelA fusion proteins and the characterization of pathways that are regulating the transcriptional activity of NF-κB by regulatory phosphorylations. As NF-κB’s central role in human physiology prohibits its global inhibition, these auxiliary or cell type-specific NF-κB regulating pathways are potential therapeutic targets. Full article

(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches)

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13 pages, 609 KiB

Open AccessReview

VHL and Hypoxia Signaling: Beyond HIF in Cancer

by Jing Zhang and Qing Zhang

Biomedicines 2018, 6(1), 35; https://doi.org/10.3390/biomedicines6010035 - 19 Mar 2018

Cited by 86 | Viewed by 17239

Abstract

Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome [...] Read more.

Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-κB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer. Full article

(This article belongs to the Special Issue Hypoxia)

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14 pages, 243 KiB

Open AccessConference Report

Update in Systemic and Targeted Therapies in Gastrointestinal Oncology

by Nelson S. Yee

Biomedicines 2018, 6(1), 34; https://doi.org/10.3390/biomedicines6010034 - 16 Mar 2018

Cited by 14 | Viewed by 6425

Abstract

Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented [...] Read more.

Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented. The use of peri-operative chemotherapy comprised of 5-fluorouracil or capecitabine, leucovorin, oxaliplatin, and docetaxel (FLOT), and immunotherapy including pembrolizumab, nivolumab, and ipilimumab in gastroesophageal carcinoma are discussed. Data from clinical trials that investigated the targeted therapeutics including nivolumab, ramucirumab, lenvatinib, and BLU-554 are reported. The role of adjuvant capecitabine in resected biliary tract carcinoma (BTC) and nab-paclitaxel in combination with gemcitabine and cisplatin in advanced BTC are presented. In colorectal carcinoma, the efficacy of nivolumab, adjuvant FOLFOX or CAPOX, irinotecan/cetuximab/vemurafenib, and trifluridine/tipiracil/bevacizumab, is examined. In summary, some of the above systemic therapies have become or are expected to become new standard of care, while the others demonstrate the potential of becoming new treatment options. Full article

(This article belongs to the Special Issue Cancer Biomarkers and Targets in Digestive Organs)

13 pages, 208 KiB

Open AccessReview

Oncolytic Adenoviruses in Gastrointestinal Cancers

by Raquel T. Yokoda, Bolni M. Nagalo and Mitesh J. Borad

Biomedicines 2018, 6(1), 33; https://doi.org/10.3390/biomedicines6010033 - 11 Mar 2018

Cited by 9 | Viewed by 6134

Abstract

Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, [...] Read more.

Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, resulting in limited improvement in survival rates in these patients. Oncolytic adenoviruses are being developed to address gastrointestinal malignancies. Each platform has evolved to maximize tumor-cell killing potency while minimizing toxicities. Tumor-specific bioengineered adenoviruses using chimeric promoters, prodrug convertase enzymes, lethal genes, tumor suppressor genes, and pseudo-typed capsids can provide the innovations for eventual success of oncolytic virotherapy. This article will review the developments in adenoviral platforms in the context of specific gastrointestinal cancers. From the bench to the implementation of clinical trials, this review aims to highlight advances in the field from its early days to the current state of affairs as it pertains to the application of adenoviral oncolytic therapy to gastrointestinal cancers. Full article

(This article belongs to the Special Issue Adenoviruses: From Virus to Medicine)

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14 pages, 805 KiB

Open AccessReview

Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets

by Lionel Kankeu Fonkoua and Nelson S. Yee

Biomedicines 2018, 6(1), 32; https://doi.org/10.3390/biomedicines6010032 - 9 Mar 2018

Cited by 42 | Viewed by 7454

Abstract

Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker [...] Read more.

Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated. Full article

(This article belongs to the Special Issue Cancer Biomarkers and Targets in Digestive Organs)

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19 pages, 1413 KiB

Open AccessReview

CD117/c-kit in Cancer Stem Cell-Mediated Progression and Therapeutic Resistance

by Brittni M. Foster, Danish Zaidi, Tyler R. Young, Mary E. Mobley and Bethany A. Kerr

Biomedicines 2018, 6(1), 31; https://doi.org/10.3390/biomedicines6010031 - 8 Mar 2018

Cited by 91 | Viewed by 17072

Abstract

Metastasis is the primary cause of cancer patient morbidity and mortality, but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patient tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven [...] Read more.

Metastasis is the primary cause of cancer patient morbidity and mortality, but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patient tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven by a cancer stem-like cell or tumor progenitor cell, while recurrence at a secondary site is driven by metastatic cancer stem cells or metastasis-initiating cells. Ongoing efforts are aimed at identifying and characterizing these stem-like cells driving recurrence and metastasis. One potential marker for the cancer stem-like cell subpopulation is CD117/c-kit, a tyrosine kinase receptor associated with cancer progression and normal stem cell maintenance. Further, activation of CD117 by its ligand stem cell factor (SCF; kit ligand) in the progenitor cell niche stimulates several signaling pathways driving proliferation, survival, and migration. This review examines evidence that the SCF/CD117 signaling axis may contribute to the control of cancer progression through the regulation of stemness and resistance to tyrosine kinase inhibitors. Full article

(This article belongs to the Special Issue Stem Cells and Cancer Therapeutics)

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12 pages, 234 KiB

Open AccessReview

The Repertoire of Adenovirus in Human Disease: The Innocuous to the Deadly

by Subrat Khanal, Pranita Ghimire and Amit S. Dhamoon

Biomedicines 2018, 6(1), 30; https://doi.org/10.3390/biomedicines6010030 - 7 Mar 2018

Cited by 114 | Viewed by 12905

Abstract

Adenoviridae is a family of double-stranded DNA viruses that are a significant cause of upper respiratory tract infections in children and adults. Less commonly, the adenovirus family can cause a variety of gastrointestinal, ophthalmologic, genitourinary, and neurologic diseases. Most adenovirus infections are self-limited [...] Read more.

Adenoviridae is a family of double-stranded DNA viruses that are a significant cause of upper respiratory tract infections in children and adults. Less commonly, the adenovirus family can cause a variety of gastrointestinal, ophthalmologic, genitourinary, and neurologic diseases. Most adenovirus infections are self-limited in the immunocompetent host and are treated with supportive measures. Fatal infections can occur in immunocompromised patients and less frequently in the healthy. Adenoviral vectors are being studied for novel biomedical applications including gene therapy and immunization. In this review we will focus on the spectrum of adenoviral infections in humans. Full article

(This article belongs to the Special Issue Adenoviruses: From Virus to Medicine)

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11 pages, 514 KiB

Open AccessReview

Role of Akt Isoforms Controlling Cancer Stem Cell Survival, Phenotype and Self-Renewal

by Sergio Rivas, Carla Gómez-Oro, Inés M. Antón and Francisco Wandosell

Biomedicines 2018, 6(1), 29; https://doi.org/10.3390/biomedicines6010029 - 7 Mar 2018

Cited by 38 | Viewed by 5668

Abstract

The cancer stem cell (CSC) hypothesis suggests that tumours are maintained by a subpopulation of cells with stem cell properties. Although the existence of CSCs was initially described in human leukaemia, less evidence exists for CSCs in solid tumours. Recently, a CD133+ cell [...] Read more.

The cancer stem cell (CSC) hypothesis suggests that tumours are maintained by a subpopulation of cells with stem cell properties. Although the existence of CSCs was initially described in human leukaemia, less evidence exists for CSCs in solid tumours. Recently, a CD133+ cell subpopulation was isolated from human brain tumours exhibiting stem cell properties in vitro as well as the capacity to initiate tumours in vivo. In the present work, we try to summarize the data showing that some elements of the Phosphoinositide 3-kinase Class I (PI3K)/ Thymoma viral oncogene protein kinase (Akt) pathway, such the activity of PI3K Class I or Akt2, are necessary to maintain the CSC-like phenotype as well as survival of CSCs (also denoted as tumour-initiating cells (TICs)). Our data and other laboratory data permit a working hypothesis in which each Akt isoform plays an important and specific role in CSC/TIC growth, self-renewal, maintaining survival, and epithelial-mesenchymal transition (EMT) phenotype, not only in breast cancer, but also in glioma. We suggest that a more complete understanding is needed of the possible roles of isoforms in human tumours (iso-signalling determination). Thus, a comprehensive analysis of how hierarchical signalling is assembled during oncogenesis, how cancer landmarks are interconnected to favour CSC and tumour growth, and how some protein isoforms play a specific role in CSCs to ensure that survival and proliferation must be done in order to propose/generate new therapeutic approaches (alone or in combination with existing ones) to use against cancer. Full article

(This article belongs to the Special Issue Stem Cells and Cancer Therapeutics)

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13 pages, 519 KiB

Open AccessReview

Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells

by Sandra Jordaan, Olusiji A. Akinrinmade, Thomas Nachreiner, Christian Cremer, Krupa Naran, Shivan Chetty and Stefan Barth

Biomedicines 2018, 6(1), 28; https://doi.org/10.3390/biomedicines6010028 - 5 Mar 2018

Cited by 25 | Viewed by 6417

Abstract

Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while [...] Read more.

Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP). However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell’s metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents. Full article

(This article belongs to the Special Issue Immuno-Active Cancer Therapeutics)

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9 pages, 206 KiB

Open AccessReview

The Application of Gene Expression Profiling in Predictions of Occult Lymph Node Metastasis in Colorectal Cancer Patients

by Noshad Peyravian, Pegah Larki, Ehsan Gharib, Ehsan Nazemalhosseini-Mojarad, Fakhrosadate Anaraki, Chris Young, James McClellan, Maziar Ashrafian Bonab, Hamid Asadzadeh-Aghdaei and Mohammad Reza Zali

Biomedicines 2018, 6(1), 27; https://doi.org/10.3390/biomedicines6010027 - 2 Mar 2018

Cited by 22 | Viewed by 4496

Abstract

A key factor in determining the likely outcome for a patient with colorectal cancer is whether or not the tumour has metastasised to the lymph nodes—information which is also important in assessing any possibilities of lymph node resection so as to improve survival. [...] Read more.

A key factor in determining the likely outcome for a patient with colorectal cancer is whether or not the tumour has metastasised to the lymph nodes—information which is also important in assessing any possibilities of lymph node resection so as to improve survival. In this review we perform a wide-range assessment of literature relating to recent developments in gene expression profiling (GEP) of the primary tumour, to determine their utility in assessing node status. A set of characteristic genes seems to be involved in the prediction of lymph node metastasis (LNM) in colorectal patients. Hence, GEP is applicable in personalised/individualised/tailored therapies and provides insights into developing novel therapeutic targets. Not only is GEP useful in prediction of LNM, but it also allows classification based on differences such as sample size, target gene expression, and examination method. Full article

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14 pages, 3528 KiB

Open AccessFeature PaperReview

Immune Monitoring of Cancer Patients Prior to and During CTLA-4 or PD-1/PD-L1 Inhibitor Treatment

by Antje Tunger, Maximilian Kießler, Rebekka Wehner, Achim Temme, Friedegund Meier, Michael Bachmann and Marc Schmitz

Biomedicines 2018, 6(1), 26; https://doi.org/10.3390/biomedicines6010026 - 1 Mar 2018

Cited by 17 | Viewed by 6869

Abstract

Targeting the immune checkpoint receptors cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) represents a very attractive treatment modality for tumor patients. The administration of antibodies against these receptors can promote [...] Read more.

Targeting the immune checkpoint receptors cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) represents a very attractive treatment modality for tumor patients. The administration of antibodies against these receptors can promote efficient antitumor effects and can induce objective clinical responses in about 20–40% patients with various tumor types, accompanied by improved survival. Based on their therapeutic efficiency, several antibodies have been approved for the treatment of tumor patients. However, many patients do not respond to checkpoint inhibitor therapy. Therefore, the identification of biomarkers is required to guide patient selection for this treatment modality. Here, we summarize recent studies investigating the PD-L1 expression or mutational load of tumor tissues as well as the frequency and phenotype of immune cells in tumor patients prior to and during CTLA-4 or PD-1/PD-L1 inhibitor treatment. Full article

(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)

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18 pages, 928 KiB

Open AccessReview

The Peripheral and Intratumoral Immune Cell Landscape in Cancer Patients: A Proxy for Tumor Biology and a Tool for Outcome Prediction

by Annette Schnell, Christian Schmidl, Wolfgang Herr and Peter J. Siska

Biomedicines 2018, 6(1), 25; https://doi.org/10.3390/biomedicines6010025 - 24 Feb 2018

Cited by 23 | Viewed by 5947

Abstract

Functional systemic and local immunity is required for effective anti-tumor responses. In addition to an active engagement with cancer cells and tumor stroma, immune cells can be affected and are often found to be dysregulated in cancer patients. The impact of tumors on [...] Read more.

Functional systemic and local immunity is required for effective anti-tumor responses. In addition to an active engagement with cancer cells and tumor stroma, immune cells can be affected and are often found to be dysregulated in cancer patients. The impact of tumors on local and systemic immunity can be assessed using a variety of approaches ranging from low-dimensional analyses that are performed on large patient cohorts to multi-dimensional assays that are technically and logistically challenging and are therefore confined to a limited sample size. Many of these strategies have been established in recent years leading to exciting findings. Not only were analyses of immune cells in tumor patients able to predict the clinical course of the disease and patients’ survival, numerous studies also detected changes in the immune landscape that correlated with responses to novel immunotherapies. This review will provide an overview of established and novel tools for assessing immune cells in tumor patients and will discuss exemplary studies that utilized these techniques to predict patient outcomes. Full article

(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)

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11 pages, 536 KiB

Open AccessArticle

Carcinoembryonic Antigen Serum Levels in Nonmelanoma Skin Cancer

by Saverio Latteri, Vito Emanuele Catania, Giulia Malaguarnera, Andrea Peri, Gaetano Bertino, Giuseppe Frazzetto, Antonio Maria Borzì, Antonio Biondi, Rosario Emanuele Perrotta and Michele Malaguarnera

Biomedicines 2018, 6(1), 24; https://doi.org/10.3390/biomedicines6010024 - 23 Feb 2018

Cited by 11 | Viewed by 4656

Abstract

Background: Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in the foetal colon, some benign conditions and different malignancies, particularly in colon adenocarcinoma. We focused this study on non-melanoma skin cancer (NMSC). NMSC is a common malignancy and it is an important [...] Read more.

Background: Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in the foetal colon, some benign conditions and different malignancies, particularly in colon adenocarcinoma. We focused this study on non-melanoma skin cancer (NMSC). NMSC is a common malignancy and it is an important source of morbidity and death in the world. In this study we evaluated whether CEA level increases in NMSC. Patients and Methods: A total of 566 patients with non-melanoma skin cancer (NMSC) were enrolled; 286 patients with NMSC showed CEA levels above normal values, and 280 showed CEA levels below normal values. Patients with high levels of CEA underwent abdominal ultrasound, gastro endoscopy, colonoscopy, and abdominal CT scans. Results: We studied 566 patients, 286 were positive to CEA and 280 were negative. Of the 286 patients positive to CEA, 132 had basal cell carcinoma (64 patients had an associated cancer) and 154 had squamous cell carcinoma (75 patients were affected by cancer). Of the 280 patients negative to CEA, 130 had basal cell carcinoma (12 were associated with cancer), and 150 had squamous cell carcinoma (18 were associated with cancer). The mean age of the 566 case control subjects were 65–81 years. Of the 10 subjects that were the positive control for CEA, two had cancer. Of the 556 subjects that were the negative control for CEA, three had cancer. Conclusions: In patients that present high serum levels of CEA, we give attention to adenocarcinoma tumour first. The pattern of association may be attributable to bias because the group with NMSC were frequently evaluated than those with no history of NMSC. Our results showed that out of 286 patients that were CEA-positive, 139 had cancer, and of the 280 that were CEA-negative, 30 had cancer. Therefore, 20% of patients do not follow the trend. Other markers should be investigated. Full article

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11 pages, 1130 KiB

Open AccessArticle

GJA4/Connexin 37 Mutations Correlate with Secondary Lymphedema Following Surgery in Breast Cancer Patients

by Mahrooyeh Hadizadeh, Seiied Mojtaba Mohaddes Ardebili, Mansoor Salehi, Chris Young, Fariborz Mokarian, James McClellan, Qin Xu, Mohammad Kazemi, Elham Moazam, Behzad Mahaki and Maziar Ashrafian Bonab

Biomedicines 2018, 6(1), 23; https://doi.org/10.3390/biomedicines6010023 - 22 Feb 2018

Cited by 18 | Viewed by 6112

Abstract

Lymphedema is a condition resulting from mutations in various genes essential for lymphatic development and function, which leads to obstruction of the lymphatic system. Secondary lymphedema is a progressive and incurable condition, most often manifesting after surgery for breast cancer. Although its causation [...] Read more.

Lymphedema is a condition resulting from mutations in various genes essential for lymphatic development and function, which leads to obstruction of the lymphatic system. Secondary lymphedema is a progressive and incurable condition, most often manifesting after surgery for breast cancer. Although its causation appears complex, various lines of evidence indicate that genetic predisposition may play a role. Previous studies show that mutations in connexin 47 are associated with secondary lymphedema. We have tested the hypothesis that connexin 37 gene mutations in humans are associated with secondary lymphedema following breast cancer surgery. A total of 2211 breast cancer patients were screened and tested for reference single nucleotide polymorphisms (SNPs) of the GJA4 gene (gap junction protein alpha 4 gene). The results presented in this paper indicate that two SNPs in the 3’ UTR (the three prime untranslated region) of the GJA4 gene are associated with an increased risk of secondary lymphedema in patients undergoing breast cancer treatment. Our results provide evidence of a novel genetic biomarker for assessing the predisposition to secondary lymphedema in human breast cancer patients. Testing for the condition-associated alleles described here could assist and inform treatment and post-operative care plans of breast cancer patients, with potentially positive outcomes for the management of disease progression. Full article

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25 pages, 698 KiB

Open AccessReview

Targeting Leukemia Stem Cells in the Bone Marrow Niche

by Sarah K. Tasian, Martin Bornhäuser and Sergio Rutella

Biomedicines 2018, 6(1), 22; https://doi.org/10.3390/biomedicines6010022 - 21 Feb 2018

Cited by 16 | Viewed by 8947

Abstract

The bone marrow (BM) niche encompasses multiple cells of mesenchymal and hematopoietic origin and represents a unique microenvironment that is poised to maintain hematopoietic stem cells. In addition to its role as a primary lymphoid organ through the support of lymphoid development, the [...] Read more.

The bone marrow (BM) niche encompasses multiple cells of mesenchymal and hematopoietic origin and represents a unique microenvironment that is poised to maintain hematopoietic stem cells. In addition to its role as a primary lymphoid organ through the support of lymphoid development, the BM hosts various mature lymphoid cell types, including naïve T cells, memory T cells and plasma cells, as well as mature myeloid elements such as monocyte/macrophages and neutrophils, all of which are crucially important to control leukemia initiation and progression. The BM niche provides an attractive milieu for tumor cell colonization given its ability to provide signals which accelerate tumor cell proliferation and facilitate tumor cell survival. Cancer stem cells (CSCs) share phenotypic and functional features with normal counterparts from the tissue of origin of the tumor and can self-renew, differentiate and initiate tumor formation. CSCs possess a distinct immunological profile compared with the bulk population of tumor cells and have evolved complex strategies to suppress immune responses through multiple mechanisms, including the release of soluble factors and the over-expression of molecules implicated in cancer immune evasion. This chapter discusses the latest advancements in understanding of the immunological BM niche and highlights current and future immunotherapeutic strategies to target leukemia CSCs and overcome therapeutic resistance in the clinic. Full article

(This article belongs to the Special Issue Stem Cells and Cancer Therapeutics)

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9 pages, 544 KiB

Open AccessCommunication

Bryonolic Acid Blocks Cancer Cell Clonogenicity and Invasiveness through the Inhibition of Fatty Acid: Cholesteryl Ester Formation

by Farid Khallouki, Robert Wyn Owen, Sandrine Silvente-Poirot and Marc Poirot

Biomedicines 2018, 6(1), 21; https://doi.org/10.3390/biomedicines6010021 - 12 Feb 2018

Cited by 12 | Viewed by 4852

Abstract

Bryonolic acid (BrA) is a pentacyclic triterpene present in several plants used in African traditional medicine such as Anisophyllea dichostyla R. Br. Here we investigated the in vitro anticancer properties of BrA. We report that BrA inhibits acyl-coA: cholesterol acyl transferase (ACAT) activity [...] Read more.

Bryonolic acid (BrA) is a pentacyclic triterpene present in several plants used in African traditional medicine such as Anisophyllea dichostyla R. Br. Here we investigated the in vitro anticancer properties of BrA. We report that BrA inhibits acyl-coA: cholesterol acyl transferase (ACAT) activity in rat liver microsomes in a concentration-dependent manner, blocking the biosynthesis of the cholesterol fatty acid ester tumour promoter. We next demonstrated that BrA inhibits ACAT in intact cancer cells with an IC₅₀ of 12.6 ± 2.4 µM. BrA inhibited both clonogenicity and invasiveness of several cancer cell lines, establishing that BrA displays specific anticancer properties. BrA appears to be more potent than the other pentacyclic triterpenes, betulinic acid and ursolic acid studied under similar conditions. The inhibitory effect of BrA was reversed by exogenous addition of cholesteryl oleate, showing that ACAT inhibition is responsible for the anticancer effect of BrA. This report reveals new anticancer properties for BrA. Full article

(This article belongs to the Special Issue Plant Derived Biomedicines)

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12 pages, 2705 KiB

Open AccessReview

Immune Landscape of Breast Cancers

by Divya Nagarajan and Stephanie E. B. McArdle

Biomedicines 2018, 6(1), 20; https://doi.org/10.3390/biomedicines6010020 - 11 Feb 2018

Cited by 85 | Viewed by 11475

Abstract

Breast cancer is a very heterogeneous disease, both at a molecular and a histological level. Five intrinsic subtypes were initially identified—Luminal-A, Luminal-B, HER2⁺, Triple negative/basal like (TNBC) and normal like—subsequently expanded to seven (Basal-like-1 and 2, mesenchymal, mesenchymal stem-like, luminal androgen [...] Read more.

Breast cancer is a very heterogeneous disease, both at a molecular and a histological level. Five intrinsic subtypes were initially identified—Luminal-A, Luminal-B, HER2⁺, Triple negative/basal like (TNBC) and normal like—subsequently expanded to seven (Basal-like-1 and 2, mesenchymal, mesenchymal stem-like, luminal androgen receptor, immuno-modulatory and unstable). Although genetic and epigenetic changes are key pathogenic events, the immune system plays a substantial role in promoting progression and metastasis. This review will discuss the extent to which immune cells can be detected within the tumor microenvironment, as well as their prognostic role and relationship with the microbiome, with an emphasis on TNBC. Full article

(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)

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10 pages, 885 KiB

Open AccessReview

Immunoconjugates for Osteosarcoma Therapy: Preclinical Experiences and Future Perspectives

by Daniele Mercatelli, Massimo Bortolotti, Alberto Bazzocchi, Andrea Bolognesi and Letizia Polito

Biomedicines 2018, 6(1), 19; https://doi.org/10.3390/biomedicines6010019 - 10 Feb 2018

Cited by 21 | Viewed by 5691

Abstract

Osteosarcoma (OS) is an aggressive osteoid-producing tumor of mesenchymal origin, which represents the most common primary bone malignancy. It is characterized by a complex and frequently uncertain etiology. The current standard care for high-grade OS treatment is neoadjuvant chemotherapy, followed by surgery and [...] Read more.

Osteosarcoma (OS) is an aggressive osteoid-producing tumor of mesenchymal origin, which represents the most common primary bone malignancy. It is characterized by a complex and frequently uncertain etiology. The current standard care for high-grade OS treatment is neoadjuvant chemotherapy, followed by surgery and post-operative chemotherapy. In order to ameliorate survival rates of patients, new therapeutic approaches have been evaluated, mainly immunotherapy with antibody-drug conjugates or immunoconjugates. These molecules consist of a carrier (frequently an antibody) joined by a linker to a toxic moiety (drug, radionuclide, or toxin). Although several clinical trials with immunoconjugates have been conducted, mainly in hematological tumors, their potential as therapeutic agents is relatively under-explored in many types of cancer. In this review, we report the immunoconjugates directed against OS surface antigens, considering the in vitro and in vivo studies. To date, several attempts have been made in preclinical settings, reporting encouraging results and demonstrating the validity of the idea. The clinical experience with glembatumumab vedotin may provide new insights into the real efficacy of antibody-drug conjugates for OS therapy, possibly giving more information about patient selection. Moreover, new opportunities could arise from the ongoing clinical trials in OS patients with unconjugated antibodies that could represent future candidates as carrier moieties of immunoconjugates. Full article

(This article belongs to the Special Issue Immunoconjugates)

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8 pages, 5014 KiB

Open AccessArticle

Photodynamic Therapy Activated by Intense Pulsed Light in the Treatment of Nonmelanoma Skin Cancer

by Domenico Piccolo and Dimitra Kostaki

Biomedicines 2018, 6(1), 18; https://doi.org/10.3390/biomedicines6010018 - 7 Feb 2018

Cited by 28 | Viewed by 12720

Abstract

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has proven to be a highly effective conservative method for the treatment of actinic keratosis (AK), Bowen’s disease (BD), and superficial basal cell carcinoma (sBCC). PDT is traditionally performed in association [...] Read more.

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has proven to be a highly effective conservative method for the treatment of actinic keratosis (AK), Bowen’s disease (BD), and superficial basal cell carcinoma (sBCC). PDT is traditionally performed in association with broad-spectrum continuous-wave light sources, such as red or blue light. Recently, intense pulsed light (IPL) devices have been investigated as an alternative light source for PDT in the treatment of nonmelanoma skin cancers (NMSC). We herein report our observational findings in a cohort of patients with a diagnosis of AK, sBCC, and BD that is treated with MAL-PDT using IPL, as well as we review published data on the use of IPL-PDT in NMSC. Full article

(This article belongs to the Special Issue Photodynamic Therapy in Cancer)

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6 pages, 178 KiB

Open AccessReview

Photodynamic Therapy in Ocular Oncology

by Maria Antonietta Blasi, Monica Maria Pagliara, Angela Lanza, Maria Grazia Sammarco, Carmela Grazia Caputo, Gabriela Grimaldi and Andrea Scupola

Biomedicines 2018, 6(1), 17; https://doi.org/10.3390/biomedicines6010017 - 7 Feb 2018

Cited by 26 | Viewed by 4755

Abstract

Although introduced for the treatment of maculopathies, photodynamic therapy (PDT) is now largely used in some eye cancers treatment. The selective tissue damage with PDT is achieved by sequestration of the photosensitizer in the target tissue and focal activation of the photosensitizer by [...] Read more.

Although introduced for the treatment of maculopathies, photodynamic therapy (PDT) is now largely used in some eye cancers treatment. The selective tissue damage with PDT is achieved by sequestration of the photosensitizer in the target tissue and focal activation of the photosensitizer by low energy directed light. In this way, it is possible to achieve the destruction of the tumor tissue by safeguarding the surrounding healthy structures. Our study describes the clinical uses and efficacy of photodynamic therapy in ocular oncology. Full article

(This article belongs to the Special Issue Photodynamic Therapy in Cancer)

9 pages, 824 KiB

Open AccessReview

BET Family Protein BRD4: An Emerging Actor in NFκB Signaling in Inflammation and Cancer

by Azadeh Hajmirza, Anouk Emadali, Arnaud Gauthier, Olivier Casasnovas, Rémy Gressin and Mary B. Callanan

Biomedicines 2018, 6(1), 16; https://doi.org/10.3390/biomedicines6010016 - 6 Feb 2018

Cited by 131 | Viewed by 11777

Abstract

NFκB (Nuclear Factor-κ-light-chain-enhancer of activated B cells) signaling elicits global transcriptional changes by activating cognate promoters and through genome-wide remodeling of cognate regulatory elements called “super enhancers”. BET (Bromodomain and Extra-Terminal domain) protein family inhibitor studies have implicated BET protein member [...] Read more.

NFκB (Nuclear Factor-κ-light-chain-enhancer of activated B cells) signaling elicits global transcriptional changes by activating cognate promoters and through genome-wide remodeling of cognate regulatory elements called “super enhancers”. BET (Bromodomain and Extra-Terminal domain) protein family inhibitor studies have implicated BET protein member BRD4 and possibly other BET proteins in NFκB-dependent promoter and super-enhancer modulation. Members of the BET protein family are known to bind acetylated chromatin to facilitate access by transcriptional regulators to chromatin, as well as to assist the activity of transcription elongation complexes via CDK9/pTEFb. BET family member BRD4 has been shown to bind non-histone proteins and modulate their activity. One such protein is RELA, the NFκB co-activator. Specifically, BRD4 binds acetylated RELA, which increases its transcriptional transactivation activity and stability in the nucleus. In aggregate, this establishes an intimate link between NFκB and BET signaling, at least via BRD4. The present review provides a brief overview of the structure and function of BET family proteins and then examines the connections between NFκB and BRD4 signaling, using the inflammatory response and cancer cell signaling as study models. We also discuss the potential of BET inhibitors for relief of aberrant NFκB signaling in cancer, focusing on non-histone, acetyl-lysine binding functions. Full article

(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches)

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4 pages, 2742 KiB

Open AccessShort Communication

Platelet-Rich Plasma (PRP) Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report

by Elisabetta Merigo, Aldo Oppici, Anna Parlatore, Luigi Cella, Fabio Clini, Matteo Fontana and Carlo Fornaini

Biomedicines 2018, 6(1), 15; https://doi.org/10.3390/biomedicines6010015 - 6 Feb 2018

Cited by 12 | Viewed by 6376

Abstract

Platelet-rich plasma (PRP) has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and keratinocyte growth factor (KGF). Oral lichen planus (OLP) is [...] Read more.

Platelet-rich plasma (PRP) has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and keratinocyte growth factor (KGF). Oral lichen planus (OLP) is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulcerative type. The properties of PRP that are supported by scientific literature in both oral medicine and other medical fields have suggested the introduction of PRP in clinical practice for the medical treatment of different soft tissues diseases, such as when OLP patients do not respond to conventional therapies, or when conventional treatments have some contraindications or side effects. The aim of this work is to describe the use of PRP used as an oral rinse for the treatment of a patient diagnosed as affected by OLP at the Dentistry, Special Needs and Maxillo-Facial Surgery Unit of the Hospital of Piacenza. PRP protocol was started after the failure of conventional therapies based on the use of topical and systemic corticosteroids, hydroxychloroquine, and low-level laser therapy applications. Full article

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11 pages, 605 KiB

Open AccessReview

Bringing the Next Generation of Immuno-Oncology Biomarkers to the Clinic

by Alessandra Cesano and Sarah Warren

Biomedicines 2018, 6(1), 14; https://doi.org/10.3390/biomedicines6010014 - 2 Feb 2018

Cited by 55 | Viewed by 14474

Abstract

The recent successes in the use of immunotherapy to treat cancer have led to a multiplicity of new compounds in development. Novel clinical-grade biomarkers are needed to guide the choice of these agents to obtain the maximal likelihood of patient benefit. Predictive biomarkers [...] Read more.

The recent successes in the use of immunotherapy to treat cancer have led to a multiplicity of new compounds in development. Novel clinical-grade biomarkers are needed to guide the choice of these agents to obtain the maximal likelihood of patient benefit. Predictive biomarkers for immunotherapy differ from the traditional biomarkers used for targeted therapies: the complexity of the immune response and tumour biology requires a more holistic approach than the use of a single analyte biomarker. This paper reviews novel biomarker approaches for the effective development of immune-oncology therapies, highlighting the promise of the advances in next-generation gene expression profiling that allow biologic information to be efficiently organized and interpreted for a maximum predictive value at the individual patient level. Full article

(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)

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11 pages, 522 KiB

Open AccessReview

The Role of Photodynamic Therapy in the Treatment of Vulvar Intraepithelial Neoplasia

by Giulio Tosti, Anna Daniela Iacobone, Eleonora Petra Preti, Sabina Vaccari, Alessia Barisani, Elisabetta Pennacchioli and Carmen Cantisani

Biomedicines 2018, 6(1), 13; https://doi.org/10.3390/biomedicines6010013 - 2 Feb 2018

Cited by 22 | Viewed by 18154

Abstract

Background: vulvar intraepithelial neoplasia is a non-invasive precursor lesion found in 50–70% of patients affected by vulvar squamous cell carcinoma. In the past, radical surgery was the standard treatment for vulvar intraepithelial neoplasia, however, considering the psychological and physical morbidities related to extensive [...] Read more.

Background: vulvar intraepithelial neoplasia is a non-invasive precursor lesion found in 50–70% of patients affected by vulvar squamous cell carcinoma. In the past, radical surgery was the standard treatment for vulvar intraepithelial neoplasia, however, considering the psychological and physical morbidities related to extensive surgery, several less aggressive treatment modalities have been proposed since the late 1970s. Photodynamic therapy is an effective and safe treatment for cutaneous non-melanoma skin cancer, with favorable cosmetic outcomes. Methods: in the present paper, the results of selected studies on photodynamic therapy in the treatment of vulvar intraepithelial neoplasia are reported and discussed. Results: Overall, complete histological response rates ranged between 20% and 67% and symptom response rates ranged between 52% and 89% according to different studies and case series. Conclusions: the real benefit of photodynamic therapy in the setting of vulvar intraepithelial neoplasia lies in its ability to treat multi-focal disease with minimal tissue destruction, preservation of vulvar anatomy and excellent cosmetic outcomes. These properties explain why photodynamic therapy is an attractive option for vulvar intraepithelial neoplasia treatment. Full article

(This article belongs to the Special Issue Photodynamic Therapy in Cancer)

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16 pages, 8613 KiB

Open AccessReview

Early and Late Onset Side Effects of Photodynamic Therapy

by Francesco Borgia, Roberta Giuffrida, Emanuela Caradonna, Mario Vaccaro, Fabrizio Guarneri and Serafinella P. Cannavò

Biomedicines 2018, 6(1), 12; https://doi.org/10.3390/biomedicines6010012 - 29 Jan 2018

Cited by 123 | Viewed by 9395

Abstract

Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. [...] Read more.

Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC) in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations. Full article

(This article belongs to the Special Issue Photodynamic Therapy in Cancer)

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11 pages, 938 KiB

Open AccessArticle

Anti-Inflammatory and Antitumor Effects of Hydroxytyrosol but Not Oleuropein on Experimental Glioma In Vivo. A Putative Role for the Renin-Angiotensin System

by María Jesús Ramírez-Expósito and José Manuel Martínez-Martos

Biomedicines 2018, 6(1), 11; https://doi.org/10.3390/biomedicines6010011 - 26 Jan 2018

Cited by 26 | Viewed by 5666

Abstract

Functional roles of the angiotensin peptides of the renin-angiotensin system (RAS) cascade can be analyzed through their corresponding proteolytic regulatory enzymes aspartyl aminopeptidase (ASAP), aminopeptidase A (APA), aminopeptidase B (APB), aminopeptidase N (APN) and insulin-regulated aminopeptidase (IRAP). These enzyme activities generate active or [...] Read more.

Functional roles of the angiotensin peptides of the renin-angiotensin system (RAS) cascade can be analyzed through their corresponding proteolytic regulatory enzymes aspartyl aminopeptidase (ASAP), aminopeptidase A (APA), aminopeptidase B (APB), aminopeptidase N (APN) and insulin-regulated aminopeptidase (IRAP). These enzyme activities generate active or inactive angiotensin peptides that alter the ratios between their bioactive forms, regulating several important processes such as the regulation of cardiovascular functions, body water regulation, normal memory consolidation and retrieval, but also cell growth, differentiation and apoptosis or the inflammatory response. We have previously described that the treatment with hydroxytyrosol but not with oleuropein or with the mixture of both compounds led to the significant inhibition of tumor growth in an in vivo glioma model by mechanisms not only related to redox balance. Using this glioma model, here we analyze the effects of the phenolic compounds oleuropein and hydroxytyrosol in circulating RAS-regulating ASAP, APA, APN, APB and IRAP specific activities and the pro-inflammatory cytokines IL-6 and TNFα to understand the relationship between the antitumor and anti-inflammatory effects of hydroxytyrosol, but not oleuropein, and the components of the RAS. We found that oleuropein increased all the activities analyzed and promoted a pro-inflammatory status, whereas hydroxytyrosol only modified ASAP and IRAP activities and promotes an anti-inflammatory status. When administrated together, oleuropein overrode the effects of hydroxytyrosol. Our results suggest a role for angiotensin III and angiotensin 1-7 in both tumor growth inhibition and anti-inflammatory response promoted by hydroxytyrosol. Full article

(This article belongs to the Special Issue Anti-inflammatory Activity of Plant Polyphenols)

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3 pages, 175 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Biomedicines in 2017

by Biomedicines Editorial Office

Biomedicines 2018, 6(1), 10; https://doi.org/10.3390/biomedicines6010010 - 16 Jan 2018

Cited by 1 | Viewed by 2633

Abstract

Peer review is an essential part in the publication process, ensuring that Biomedicines maintains high quality standards for its published papers[...] Full article

11 pages, 260 KiB

Open AccessReview

RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis

by Stéphane Mathis and Gwendal Le Masson

Biomedicines 2018, 6(1), 9; https://doi.org/10.3390/biomedicines6010009 - 15 Jan 2018

Cited by 20 | Viewed by 6021

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS. Full article

(This article belongs to the Special Issue Antisense Therapy)

12 pages, 4068 KiB

Open AccessReview

Actinic Keratosis and Non-Invasive Diagnostic Techniques: An Update

by Alice Casari, Johanna Chester and Giovanni Pellacani

Biomedicines 2018, 6(1), 8; https://doi.org/10.3390/biomedicines6010008 - 8 Jan 2018

Cited by 48 | Viewed by 9146

Abstract

Actinic keratosis represents the earliest manifestation of non-melanoma skin cancer. Because of their risk of progression to invasive squamous cell carcinoma, an earlier diagnosis and treatment are mandatory. Their diagnosis sometimes could represent a challenge even for expert dermatologists. Dermoscopy, confocal laser microscopy [...] Read more.

Actinic keratosis represents the earliest manifestation of non-melanoma skin cancer. Because of their risk of progression to invasive squamous cell carcinoma, an earlier diagnosis and treatment are mandatory. Their diagnosis sometimes could represent a challenge even for expert dermatologists. Dermoscopy, confocal laser microscopy and optical coherence tomography could help clinicians in diagnosis. Full article

(This article belongs to the Special Issue Photodynamic Therapy in Cancer)

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10 pages, 210 KiB

Open AccessReview

Stereotactic Body Radiation Therapy in the Management of Upper GI Malignancies

by Leila Tchelebi, Nicholas Zaorsky and Heath Mackley

Biomedicines 2018, 6(1), 7; https://doi.org/10.3390/biomedicines6010007 - 3 Jan 2018

Cited by 5 | Viewed by 5321

Abstract

The role of external beam radiation therapy (EBRT) in the management of upper gastrointestinal malignancies is constantly evolving. As radiation therapy techniques improve and are able to deliver more ablative doses of radiotherapy while sparing healthy tissue, radiation can be applied to a [...] Read more.

The role of external beam radiation therapy (EBRT) in the management of upper gastrointestinal malignancies is constantly evolving. As radiation therapy techniques improve and are able to deliver more ablative doses of radiotherapy while sparing healthy tissue, radiation can be applied to a wider range of clinical scenarios. Stereotactic body radiation therapy (SBRT) allows a high dose of radiation to be delivered to a highly conformal treatment volume in a short amount of time. Another potential advantage of SBRT is its ability to increase tumor immunogenicity, while also having less of an immunosuppressive effect on the patient, as compared to conventionally fractionated radiation therapy. In so doing, SBRT may potentiate the effects of immune therapy when the two treatments are combined, thus improving therapeutic outcomes. This article provides an overview of the role of SBRT in the management of upper gastrointestinal GI malignancies and the emerging data on immune biomarkers and SBRT, with a focus on pancreatic and liver cancer. Full article

(This article belongs to the Special Issue Cancer Biomarkers and Targets in Digestive Organs)

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Biomedicines, Volume 6, Issue 1 (March 2018) – 36 articles

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