Michael W. Beaury1, Megan L. Kelly-Beaury2, Gilbert Sharp3, Jessica A. Cottrell4*
Seton Hall University, South Orange, NJ, USA
Osteosarcoma is a rare but deadly cancer, predominantly affecting both adolescent and young adult populations. Osteosarcoma occurs when an aggressive malignant neoplasm arises from transformed cells of mesenchymal origin, which eventually produce a malignancy in the osteoid. Diagnosis of osteosarcoma typically results from symptoms of pain or swelling in the bone, which can be confirmed through laboratory testing of alkaline phosphatase and lactate dehydrogenase levels as well the detection of microscopic and macroscopic lesions. Pathogenesis of osteosarcoma is caused by a diverse set of factors including physical agents, radiation, chromosomal aberrations and viral infection which dysregulate cellular functions. Current research focuses on understanding how microRNAs play a role in osteosarcoma and other aggressive cancers. In this review, we discuss current treatments options including chemoresistant strategies and immunotherapies that show promise at combating osteosarcoma and other cancers.DOI: 10.29245/2578-2967/2018/2.1127 View / Download Pdf
Julia E. McGuinness1* and Katherine D. Crew1,2,3
1Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032
2Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032
3Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032
Screening mammography is recommended by U.S. medical organizations for breast cancer screening in average risk women because of its demonstrated reductions in breast cancer mortality. However, significant disparities in breast cancer screening utilization and mortality remain among racial/ethnic minorities. Efforts have appropriately been directed at increasing engagement with screening services in these populations, however, there is a dearth of data regarding false-positive rates and overdiagnosis in minority patients engaged in breast cancer screening. We recently examined screening practices among a predominantly Hispanic population presenting to an academic medical center in New York, NY, and found that approximately 53% of women experienced at least one false-positive mammography result over a median of 8.9 years of screening. We also observed that Hispanic women were more likely to screen annually than white women despite recommendations to screen less frequently. In this review, we briefly review the benefits and harms of screening mammography in average-risk women, namely, false-positive results and breast cancer overdiagnosis, followed by a discussion of the disparities in breast cancer screening and mortality among racial/ethnic minority populations. We then present our own recent observations and propose that future interventions among Hispanic and other minority populations could include patient- and provider-centered educational programs that focus on providing a balanced discussion of benefits and harms of screening mammography.DOI: 10.29245/2578-2967/2018/2.1128 View / Download Pdf
1Kang Qin, 2Helei Hou and 3*Xiaochun Zhang
1,2,3*Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China
With high morbidity and mortality, lung cancer has become the leading cause of cancer-related death worldwide, of which 85% are non-small-cell lung cancer (NSCLC). Most patients present with advanced disease at diagnosis and 5-year survival rate is no more than 30% due to lack of appropriate screening and early detection. In spite of tissue samples, ctDNA (circulating tumor DNA) is also widely used for molecular profiling to guide the treatment of NSCLC for lots of advantages. This review mainly focuses on the clinical and investigational applications of ctDNA detection in facilitating the personalized therapy of NSCLC.
Initially reported by Mandel et al. in 1948M1, cfDNA (cell-free DNA) refers to the acellular, free DNA fragments in circulation (plasma or serum) derived from somatic cells through mechanisms like necrosis, apoptosis and exosome secretion. ctDNA is cfDNA generated by tumor cells, which carries cancer-associated genetic alterations2,3. In 1977, Leon et al. first reported that the level of plasma ctDNA of patients with cancer was significantly higher than that of normal persons4, which was also confirmed in NSCLC5,6. In NSCLC patients, techniques for targetable genetic ctDNA detection have improved from traditional ARMS, HPLC, BEAMing, FISH to new generations of NGS (next generation sequencing), ddPCR and CAPP-Seq etc. Compared with traditional detection methods, NGS shows extraordinary advantages like massively parallel sequencing, lower-inputs, cost-effectivity, ultra-sensitivity and hyper accuracy7,8. The main applications of ctDNA detection in the personalized treatment of NSCLC patients will be discussed in this review.DOI: 10.29245/2578-2967/2018/2.1121 View / Download Pdf
Richard Sleightholm BS1 and Michael J Baine MD PhD2*
1Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA
2*Department of Radiation Oncology, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
Concurrent chemoradiotherapy plays a vital role in the treatment of locally advanced squamous cell carcinoma of the oropharynx (LA-OPC). Importantly, only 50-85% of patients undergoing this treatment are able to complete their prescribed chemotherapy courses due to treatment-associated morbidity. The significance of chemotherapy completion, or lack thereof, remains unknown in this setting. To further investigate if chemotherapy non-completion affects patient outcomes, a single institutional retrospective study was undertaken analyzing 73 patients undergoing definitive radiation for LA-OPC and revealed a near-significant trend toward improved overall survival on multivariable analysis (p=0.053) in those completing chemotherapy. We are presently providing a commentary on this manuscript in an attempt to provide context and further interpretation of the presented results as well as suggest areas in need of additional investigation.DOI: 10.29245/2578-2967/2018/2.1125 View / Download Pdf
DHealthPsych, Pines and Steps Southmead Hospital North Bristol Hospital Trust, Bristol, United Kingdom
Head and neck cancer (HNC) carry a high level of morbidity and mortality, but the impact of HNC on survivors differs widely among individuals, and a significant number of them suffer from negative psychological effects of the disease. However, some people report a significant positive effect of experiencing HNC and its treatment.
This review looks at demographic, clinical and psychological factors associated with positive psychological change (PPC) in HNC populations.
Eight quantitative manuscripts were identified as reporting on PPC in HNC. These studies were split between recruiting participants via cancer clinics and postal surveys, and the majority use a cross-sectional study design.
Demographic factors across the papers showed similar patterns of relationships across PPC; that higher education/qualification and cohabitation/marriage are associated with increased PPC. Limited research reported longitudinal patterns of change and showed that for people with lower stage tumours and those who only had a surgical intervention greater PPC developed over time. Multivariable modeling adjusting for psychosocial variables found that PPC had a quadratic relationship with time since diagnosis, increasing initially and leveling off after 18 months.
Further research would aid the identification of bio-psychosocial factors that influence the development of PPC and inform the development of rehabilitation interventions while enabling consideration of the natural development of the phenomenon.DOI: 10.29245/2578-2967/2018/2.1126 View / Download Pdf
Wataru Nakajima and Nobuyuki Tanaka*
Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, Japan
Evasion of apoptosis is one of the typical hallmarks of cancer and a major mechanism for cancer development, tumor growth, and acquisition of resistance to chemotherapy. The anti-apoptotic Bcl-2 protein family, particularly MCL1 and BCL-XL, play an important role in acquisition of apoptosis evasion. MCL1 is a highly unstable protein that is constantly degraded by the ubiquitin-proteasome system. An increase in MCL1 protein has been reported in many cancers, including lung cancer, through high mRNA expression or impairment of its degradation systems. To date, much evidence has shown that MCL1 is important for cancer cell survival and drug resistance in lung cancers. In this review, we discuss the role and mechanism of high MCL1 expression in lung cancer.DOI: 10.29245/2578-2967/2018/1.1123 View / Download Pdf
Edwin Roger Parra
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Multiplexed immunofluorescence (IF) methods to detect simultaneously different molecules are revolutionizing immunohistochemistry (IHC) in the last years. These new technologies can be valuable for tumor examination in formalin-fixed paraffin-embedded (FFPE) specimens, and for improved new treatment discoveries and translational cancer studies. The aim of this mini-review is to highlight the recent methodologies that using multiplexed IF to study simultaneous proteins identification in FFPE tumor tissues to clinical research and potential translational analysis. Multiplexed IF methods, which permit the identification of up to 4 proteins at the same time, have been increased in the last years the abilities of study cells by cells and their spatial distribution in several tumor tissues. Although, most of the old platforms are not more used after the powerful multiplex IHC methods are continue growing, the basis of these old methodologies have helped to improve the new technologies. Associated with image analysis software’s these technologies can be improved to performance high throughput assay to study these specimens. Each multiplexed IF technique, detailed herein, is associated with important advantages in cancer study as well as translational research studies.DOI: 10.29245/2578-2967/2018/1.1122 View / Download Pdf
Soham Datta1,2, Binyao Yang2, Jiachun Lu1,2 *
1The State Key Lab of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, China.
2The School of Public Health, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou, 510182, China
Lung cancer being one of the leading causes of cancer-related deaths around the world has significantly added to the global burden of disease. Late diagnosis, unavailability of definitive treatment and an unclear pathophysiological mechanism behind the role of various genes expressed in lung cancer make it a challenge that needs new techniques and better understanding of the underlying pathology and role of genetics. Long non coding RNAs, once considered insignificant, are now being elucidated to have major roles to play in the regulation and development of carcinogenesis. In this review, the ability of a lncRNA, lncRNA IGFBP4-1 to modulate cellular metabolic processes, eventually affecting lung cancer progression and consequently being a potential biomarker for lung cancer diagnosis has been discussed.DOI: 10.29245/2578-2967/2018/1.1116 View / Download Pdf
Estefanía Nova-Lamperti1,2*, Marco Fraga1, Marco Romano3, Giovanna Lombardi3#
1Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, 4070386. Concepcion, Chile
2PreveGen Laboratory, Chacabuco 556, Concepcion, Chile
3MRC Centre for Transplantation, School of Immunology & Microbial Sciences, King’s College London, Guy’s Hospital, SE1 9RT. London, United Kingdom
Regulatory CD4+T-cells have been recently classified as regulatory T helper (Th)-like cells according to the expression of specific transcription factors, cytokines and chemokine receptors that mirror effector Th lineages. In our report: “An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment” we found that Th2-like Tregs were increased in the tumour microenvironment in comparison with Th1-like, Th17-like and Th1/Th17-like Tregs. In addition, despite similar expression of CCR4 between all Tregs subtypes, Th2-like Tregs migrated more toward CCL17 and CCL22, and expressed higher levels of CCR8 than the other Th-like Tregs. Other studies have characterised human tissue-infiltrating Tregs and demonstrated that CCR8 is the main chemokine receptor differentially expressed in Tregs isolated from malignant tissues in comparison with healthy tissues. Given that CCR8 is a marker of Th2 lineages it is possible that Th2-like Tregs and CCR8+ Tregs are the same population of cells involved in tumour progression. However, whether they are recruited or differentiated in situ by the tumour microenvironment is still unknown. In this mini review, we describe the role of the different Th subsets in health and cancer and we present the different hypotheses about the presence of Th2-like Tregs in the tumorigenic environments.DOI: 10.29245/2578-2967/2018/1.1119 View / Download Pdf
Atsushi Okabe1, Atsushi Kaneda1*
1Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Cancer arises through the accumulation of genetic and epigenetic alterations. Comprehensive analyses of human cancer epigenomes over the past decade have revealed that chromatin and epigenetic aberrations induced by genetic, metabolic, and environmental stimuli play important roles in tumor initiation as well as progression. Among these aberrations, DNA hypermethylation at promoter regions is one of the major mechanisms to silence tumor suppressor genes in cancer, and has been studied in detail. For gastric cancer, for example, we and other groups have conducted genome-wide DNA methylation analyses, and classified gastric cancer into several DNA methylation epigenotypes. Gastric cancer with Epstein-Barr virus (EBV) infection exhibits the most extensive hypermethylation phenotype among all the human malignancies, and EBV infection itself is shown to cause aberrant DNA methylation induction. EBV infection also alters histone modifications, not only at promoter regions but also at enhancer regions. Epigenetic alteration at enhancers causes aberrant regulation of cancer-related genes together with epigenetic alteration at promoters, and it is known to contribute to tumorigenesis. We here review epigenetic aberration at enhancer regions in gastric cancer.DOI: 10.29245/2578-2967/2018/1.1120 View / Download Pdf
Julie-Ann O’Reilly1*, Richard J. O’Kennedy1,2
Prostate cancer (PCa) incidence is increasing due to the ageing worldwide population. In recent years, the unsuitability of prostate specific antigen (PSA) as a diagnostic biomarker has become apparent. Unnecessary treatment of men with non-lethal disease leading to significant quality-of-life reducing side-effects resulted in 2017 in the US Preventative Services Task Force (USPSTF) recommending selective and limited use of PSA testing for PCa. An immediate need exists for a test capable of accurate and early diagnosis of PCa. Critically, this test must differentiate between indolent and aggressive PCa to inform appropriate management of the disease. The key to predictive accuracy is the utilisation of combinations of diverse biomarkers and clinical data. A number of suitable new tests have emerged since 2013 but none of these have been implemented in the clinical setting. Extensive clinical validation of these tests is critical to address the chasm that now exists in PCa diagnostics. This mini review assesses current clinical issues for PCa diagnosis, evaluates currently available commercial tests and critically assesses next-generation diagnostic tools that could revolutionise PCa diagnostics.DOI: 10.29245/2578-2967/2018/1.1111 View / Download Pdf
The major theme throughout this paper was solving the problem of multidrug resistance (MDR) in chemotherapeutic remediation for breast cancer patients by an aptamer-labeled hybrid nanoparticle to enhance selective delivery of siRNA into tumor cells and produce an enhanced knock-down of P-glycoprotein (P-gp); which was detected mainly by western blot. The primary focus of this study was to know whether labeling nanoparticles with a cancer cell specific aptamer could enhance selective delivery of siRNA into tumor cells leading to enhanced knock-down of P-glycoprotein or P-gp as compared to non-labeled nanoparticles. The goal is to minimize cancerous gene expression by silencing its mRNA. Target specificity is not only key in completing this goal, but it is also necessary regarding, biodegradability, cytotoxicity and immune response. To accomplish this goal, the design methods had to be meticulous and carefully researched andapplied.DOI: 10.29245/2578-2967/2018/1.1103 View / Download Pdf
Ashenafi Bulle1, Jeroen Dekervel1, Schalk van der Merwe2, Eric Van Cutsem1, Chris Verslype1 and Jos van Pelt1*
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most lethal tumor around the world and stands out from many other cancers. Despite increasing research for better diagnostic and treatment strategies, there has hardly been a substantial improvement over the last decades in the 5-year survival. This is mainly because, at the time of diagnosis, the cancer cells have already migrated and invaded distant organs and tissues. At this stage, patients in most cases are ineligible for surgery and their response to conventional therapies, such as radiotherapy and chemotherapy, is also very poor.
Researchers have mainly been targeting the genetic alterations of the cancer cells, and these genetic therapies in pancreatic cancer have significantly failed to improve patient survival. It is true that the early stages of tumor formation are based on a combination of genetic and epigenetic alterations that activate oncogenes and/or inhibit tumor suppressor genes, but progress in PDAC is mainly orchestrated by microenvironmental factors. Recently, targeting tumor microenvironment components that play a prominent role in tumor progression (fibrous tissue, angiogenesis, hypoxia, tumor-associated macrophages, etc.) have begun to attract the focus of cancer researchers. In addition, immunotherapy, which has shown some success in other types of cancer, is now also emerging for pancreatic cancer for which the microenvironment possess specific challenges.
This review highlights current obstacles and opportunities in pancreatic cancer research and treatment (in vitro and in vivo (patient-derived tumor xenografts and genetic engineered mouse models)) and also indicates future directions to be explored as a potential strategy to improve patient outcomes.DOI: 10.29245/2578-2967/2018/1.1112 View / Download Pdf
Jaroslaw Lewandowski and Maciej K Kurpisz*
The first clinical trials subdued optimistic forecasts of the rapid use of iPSC technology across a large spectrum of diseases. However, positive safety results originating from administration of differentiated ESCs to first patients can be treated as the promise to future of this regenerative medicine branch. Advances in non-viral methods for pluripotency induction, including episomal and mRNA strategies as well as microRNA switches robustly purifying heterogeneous differentiated PSCs may accelerate further progress. In the present decade the development of an effective genome editing including CRISPR/Cas9, novel therapeutic approach and intensive research in 3D in vitro culture systems including tissue engineering can further expand the potential of iPSCs. The herein mini-review article extends and updates the current approaches in state-of-the-art techniques of human embryonic stem cell and induced pluripotent stem cell derivation.DOI: 10.29245/2578-2967/2018/1.1104 View / Download Pdf
Christina Ng Van Tze1*, Henry Fitzgerald2, Akhtar Qureshi3, Huck Joo Tan3, May Lee Low4, Mun Kit Lim4, Vui Chee Lo1
Colorectal cancer is a major cause of morbidity and mortality worldwide. It has been identified as the most common cancer in men and second most common cancer in women in Malaysia. This mini-review is meant to present the current state and overview of colorectal cancer in Malaysia. Our efforts through EMPOWERED, The Cancer Advocacy Society of Malaysia to reduce the toll of colorectal cancer through a customised annual Colorectal Cancer Awareness, Screening and Treatment Project with high compliances are also briefly summarised.DOI: 10.29245/2578-2967/2018/1.1109 View / Download Pdf
Assistance Publique des Hôpitaux de Paris, Avenue Victoria 75003 Paris, France
A first patient with metastatic adenocarcinoma of the pancreas has decided, on his own, to refuse chemotherapy but to treat himself with lipoïc acid, hydroxycitrate combined with oral ingestion of chlorine dioxide. His blood tests and radiological examinations have almost normalized and the disease is stable at 18 months. Another patient with hormone resistant metastatic prostate cancer has experienced a sharp drop in PSA level as well as improved medical condition. From extensive literature review, the mechanism of action of chlorine dioxide is unknown. It is our hypothesis (albeit unproven) that chlorine dioxide results in tumor cell acidification of the alkaline pH of cancer cells.DOI: 10.29245/2578-2967/2018/1.1107 View / Download Pdf