Glycosylation in Cancer: From Functional Roles to Therapeutic Implications

A novel multifunctional superparamagnetic iron oxide nanoparticles (SPIONs, chemically Fe3O4) conjugated with carboxymethyl sago cellulose, and 5-fluorouracil (Fe3O4-CMSC-5FU) was synthesized for the treatment and diagnosis of cancer. The nano size of conjugated nanoparticles restricts its entry only to cancer cells (because of its leaky vasculature) and the magnetic property of SPIONs, could localize the nanoparticle conjugate at the target area by applying external magnets. The CMSP conjugation in the nanoparticles helps in achieving pH dependent release. Ideally, the nanoparticle should show no release in the blood (pH 7.4) and selective release in cancer cells (pH 5.4). SPIONs generate heat upon exposure to laser lights, and this photothermic effect could be exploited to kill cancer cells. Also, SPIONs are an excellent contrasting agent and useful in identifying cancer cells by CT scan. The Fe3O4-CMSC-5FU nanoparticles were synthesized using the solvothermal method and chemical conjugation. The XRD pattern of these nanoparticles showed the crystalline nature of Fe3O4 and 5-FU. The conjugation of Fe3O4 nanoparticles to carboxymethyl sago cellulose (CMSC) was confirmed using EDX and FTIR. The presence of Fe3O4 in the nanoparticles is also evident from STEM. Elemental analysis of conjugate nanoparticles using FESEM indicated the presence of fluorine, which could confirm the presence of 5FU. In addition, TGA also confirms the loading of the drug into the SPIONs-CMSP conjugate nanoparticle. The drug loading efficiency of 5-FU was found to be 10 to 84% w/w. In vitro drug release study was conducted at 37o C using a dialysis membrane which contains nanoparticle complex and immersed in the release medium at different pH (5.4 and 7.2). Samples were collected at distinct intervals, and the amount of drug released were analyzed spectrophotometrically. The release of the drug was observed only at pH 5.4, which is relevant for cancer cells. Cytotoxicity and biocompatibility studies showed that the novel nanoparticle formulation is non-toxic towards healthy cells but destroys the cancer cells due to its pH-dependent release profile. In vivo, studies using mice model confirmed the efficiency of the nanoparticles in delivering 5-FU only to cancer cells. Further, the anticancer effect enhanced by hyperthermia, which kills cancer cells due to elevated temperature via external stimuli of SPIONs using laser light. The combination of hyperthermia and targeted delivery of 5-FU was observed efficient compared to the individual treatments. Targeted and controlled release of the drug from the proposed delivery vehicle along with photo-thermal therapy (hyperthermia) looks promising in selectively killing cancer cells. Also, these nanoparticles can act as useful CT imaging tools in diagnosing the tumor location and monitoring prognosis of the therapy. The focus of this work is to use multifunctional Fe3O4-CMSC-5FU nanoparticle conjugate for oncological applications, with emphasis on therapeutic, diagnostic and prognostic purposes. The results have exibited Fe3O4-CMSC-5FU can effectively be used as a controlled drug delivery system owing to effective magnetic site targetting property and cancer cell traget selection of the nanopartical system.

Nanomaterials for Cancer Diagnosis

The laboratory mouse is the foremost model organism for interrogating the genetic and molecular basis of human cancer and is a powerful platform for identifying therapeutically effective targets for prevention and treatment of cancer. Research using genetically engineered mouse models (GEMMs) have led to important advances in our understanding of the genetic basis of cancer susceptibility, the function of tumor suppressors and oncogenes, and therapy responses in preclinical and co-clinical studies. Patient Derived Xenograft (PDX) models are an increasingly important model system for in vivo studies of human cancer. These models are created by implanting patient tumors into immunodeficient or humanized mouse hosts and are a powerful translational research platform for preclinical and co-clinical studies. The number of GEMM and PDX mouse models increases significantly every year and the diverse cancer-related data about human cancer models tend to be distributed in ways that makes it difficult for researchers to integrate and interpret the information to find the most relevant model for their research. The Mouse Tumor Biology database (http://tumor.informatics.jax.org) is an expertly curated resource for information and data about genetically defined mouse strains and PDX models of human cancer. MTB provides query tools to enable integrated searches and visualization of these varied data, thus facilitating the assessment of novel mouse models of human cancer and potential preventative and therapeutic treatments. Enforcement of controlled vocabularies and standard gene, allele and strain nomenclature within MTB facilitates precise and comprehensive queries of MTB for pertinent mouse models. MTB contains data from spontaneous or endogenously induced tumors from genetically defined mice including tumor classification, incidence, Quantitative Trait Loci, pathology reports, images and genetic changes in the tumor (somatic) and background strain (germline) genomes. The PDX resource enables queries based on tumor type, cancer diagnosis and genomic properties of the engrafted tumors. Information in MTB is obtained from curation of peer-reviewed scientific publications and direct data submissions from individual investigators and large-scale programs. New features in MTB include the Faceted Tumor Search Form and a Reported Mouse Models table linking the most common fatal human cancers to reported equivalent mouse models. MTB contains over 77,000 Tumor Frequencies and over 2,200 Pathology Reports with over 6,600 images from over 4,200 references. MTB provides access to detailed clinical, pathological, expression and genomics data from over 400 PDX models. Information in MTB is integrated with cancer models data from other bioinformatics resources including PathBase, the Gene Expression Omnibus and ArrayExpress. MTB is supported by NCI grant CA089713. Citation Format: Dale A. Begley, Debra M. Krupke, Steven B. Neuhauser, Joel E. Richardson, John P. Sundberg, Janan T. Eppig, Carol J. Bult. Identifying therapeutically relevant mouse and patient-derived xenograft (PDX) models of human cancer using the mouse tumor biology database (MTB) data resource [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2804. doi:10.1158/1538-7445.AM2017-2804

One of the leading causes of death in women around the word is breast cancer. For the treatment of most cancers, chemotherapy is a good option. The most treatment approaches for breast cancer are radiotherapy, surgery and chemotherapy. There are some restrictions and limitations in diagnostic approaches and treatment methods. They result in the progress of new diagnosis and treatment approaches to improve the life quality of patients. Application of nanotechnology in the treatment of cancers currently has received much attention. In cancer treatments, nanotechnology plays a significant role in the drug delivery. Tumors can be targeted by nanoparticles. They have important role in controlling the drug release to accurate sites. Therefore, nanoparticles improve the drug efficiency and reduce the normal organ’s toxicity. Another ability of nanoparticles is activation of immune cells against tumors. As a result, nanoparticles can be used as a proper and efficient tool in the treatment and diagnosis of cancer. In this review we discuss about using nanotechnology and application of different nanoparticles in diagnosis and treatment of breast cancer.

Nanotherapeutics is to apply and further develop the various nanomedicine strategies such as polymer conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles, carbon nanotubes, nanoparticles of biodegradable polymers for sustained, controlled and targeted co-delivery of diagnostic and therapeutic agents for better theranostic effects and fewer side effects. The purpose is to diagnose and treat the diseases at their earliest stage, when the diseases are most likely curable or at least treatable. Nanomedicine can be defined as application and further development of nanotechnology to solve the problems in medicine, that is, to diagnose, treat and prevent diseases at the cellular and molecular level [1]. ‘Theranostics’ refers to simultaneous integration of diagnosis and therapy. The term derived from thera(py) + (diag)nostics to merge the two fields for advanced applications [2]. Nanomedicine is to apply and further develop the various nanocarriers may include polymer conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles (i.e., noble metal, mesoporous silica nanoparticles, metal oxide, magnetic nanoparticles and quantum dots), nanocarbons and nanoparticles of biodegradable polymers for sustained, controlled and targeted co-delivery of diagnostic and therapeutic agents to diagnose and treat the diseases at their earliest stage, when the diseases are most likely curable or at least treatable [3]. It can be promising even for the fatal diseases such as cancer, cardiovascular diseases and AIDS, and creates the chance to make treatment much less troublesome and prognosis bright, thus saving resources and enhancing the quality of life for the patients [4]. Theranostic nanomedicine means colloidal nanoparticles ranging in sizes from 1 to 1000 nm (1 μm). They consist of macromolecular materials/polymers/carbon nanomaterials/metals and inorganic nanoparticles in which the diagnostic and therapeutic agents are adsorbed, conjugated, entrapped and encapsulated for diagnosis and treatment simultaneously at the cellular and molecular level. Indeed, some nanomedicines have unique physicochemical properties that show applications in diagnosis and therapy such as optical properties, hyperthermia effect and photothermal ablation. For example, gold nanoparticles, magnetic nanoparticles or carbon nanotubes have intrinsic diagnostic and therapeutic properties. They act as self theranostic nanomedicines or platforms. An ideal theranostic nanomedicine would target at the diseased site, diagnose morphology and biochemical changes of the tissue/organ of interest, provide potent/effective therapy as well as possess biocompatibility and biodegradability. The theranostics field is expected to contribute to patient healthcare and safety as personalized medicine [3,4]. This editorial was carried out with a view to summarize the recent developments of advanced theranostic nanomedicine. Theranostic nanomedicine may be defined as nanomedicine that combines therapeutics and diagnostics in a nanocarrier [3]. The therapeutic agents include chemical drugs or biological drugs (i.e., proteins and peptides). The diagnostic agents commonly Nanotheranostics: advanced nanomedicine for the integration of diagnosis and therapy

Simultaneous detection of dual biomarkers using hierarchical MoS2 nanostructuring and nano-signal amplification-based electrochemical aptasensor toward accurate diagnosis of prostate cancer

Cancer is caused by malignant cell proliferation, invasive and metastatic, which is a serious threat to human health, while early diagnosis and treatment of cancer is the key to reduce the mortality rate. In recent years, research on cancer biomarkers such as DNA, RNA, and protein has gradually attracted more and more scientists' attention, and these markers have specificity and can be specifically recognized to achieve early detection and diagnosis of cancer. Therefore, bio electrochemical sensors targeting different cancer biomarkers have been developed, which have a potential value in facilitating the diagnosis, treatment and prognosis assessment of cancer due to their advantages of high sensitivity, high selectivity, low cost, ease of manipulation and short response time. Graphene and its derivatives possess unique physicochemical properties based on their two-dimensional structure, which include thin thickness, high electrical conductivity and high thermal conductivity, good hydrophilicity, excellent biocompatibility and low toxicity, and thus graphene-based nanomaterials have been widely used in the development of such electrochemical biosensors. In this review, we summarize the properties of graphene and a series of its derivatives also including their preparation methods, introduce the types and principle of electrochemical biosensors, and outlines the value of electrochemical sensors based on graphene and its derivatives in the clinical treatment of lung cancer, hematologic malignancies, and pancreatic cancer.

Chemotherapy is the routine treatment for cancer despite the poor efficacy and associated off-target toxicity. Furthermore, therapeutic doses of chemotherapeutic agents are limited due to their lack of tissue specificity. Various developments in nanotechnology have been applied to medicine with the aim of enhancing the drug delivery of chemotherapeutic agents. One of the successful developments includes nanoparticles which are particles that range between 1 and 100 nm that may be utilized as drug delivery systems for the treatment and diagnosis of cancer as they overcome the issues associated with chemotherapy; they are highly efficacious and cause fewer side effects on healthy tissues. Other nanotechnological developments include organic nanocarriers such as liposomes which are a type of nanoparticle, although they can deviate from the standard size range of nanoparticles as they may be several hundred nanometres in size. Liposomes are small artificial spherical vesicles ranging between 30 nm and several micrometres and contain one or more concentric lipid bilayers encapsulating an aqueous core that can entrap both hydrophilic and hydrophobic drugs. Liposomes are biocompatible and low in toxicity and can be utilized to encapsulate and facilitate the intracellular delivery of chemotherapeutic agents as they are biodegradable and have reduced systemic toxicity compared with free drugs. Liposomes may be modified with PEG chains to prolong blood circulation and enable passive targeting. Grafting of targeting ligands on liposomes enables active targeting of anticancer drugs to tumour sites. In this review, we shall explore the properties of liposomes as drug delivery systems for the treatment and diagnosis of cancer. Moreover, we shall discuss the various synthesis and functionalization techniques associated with liposomes including their drug delivery, current clinical applications, and toxicology.

ObjectivesThe diagnosis and treatment of cancer are stressful events that could trigger psychological distress in a large number of cancer patients. The aim of this study was to examine the association between gastric cancer and the risk of new onset of depression among South Korean adults.MethodsData from 12,664 participants aged over 40 years was derived from the National Health Service National Sample Cohort (2002–2013). The case cohort consists of patients who received a diagnosis of gastric cancer between 2002 and 2009, and the corresponding control group was selected through 1:1 propensity score matching (case: 6332, control: 6332). The new onset of depression was considered as the dependent variable. A Cox proportional hazards regression model was built to analyze the associations between variables in consideration.ResultsIndividuals with gastric cancer had a higher risk of new onset of depression than those without cancer (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.13–1.45.) Female gastric patients had a higher risk of depression compared to male patients (Female; HR = 1.89, 95% CI = 1.66–2.16, Male; HR = 1.25, 95% CI = 1.10–1.41). Gastric cancer patients in their 60s had the highest risk of new onset of depression compared to other age groups and no cancer group (HR = 1.61, 95% CI = 1.40–1.85). Gastric cancer patients who were previously diagnosed with depression prior to their diagnosis of cancer had a higher risk of new onset of depression than gastric cancer patients without antecedent diagnosis of depression (Past Depression (Yes); HR = 5.17, 95% CI = 4.10–6.51, Past Depression (No); HR = 1.35, CI = 1.21–1.51).ConclusionsThe study identified a significant relationship between gastric cancer and depression among South Korean adults, suggesting that the diagnosis and treatment of gastric cancer increases the risk of new onset of depression, especially among female patients between 60 and 69 years old of high income and living in metropolitan regions. Pre-existing health conditions also appeared to be a risk factor. Thus, in consideration of treatment efficacy and patients’ quality of life, the results of the study emphasizes the need for attentive intervention, while distinguishing the most vulnerable groups.

As one of the diseases with high morbidity and low cure rate in the world, cancer has always threatened the health of the public. However, due to the complexity, diversity and heterogeneity of the tumor, it is difficult to inhibit tumor recurrence and metastasis by relying on surgery, radiotherapy or chemotherapy. Photothermal therapy (PTT) is a cancer treatment by laser irradiation, which converts light energy into heat energy mediated by photothermal agents, and induces local tissue hyperthermia to treat cancer. And it has attracted widespread attention because of its non-specificity, high tumor ablation efficiency, and low toxic side effects on normal cells. However, the clinical transformation process of PTT is also severely limited by some disadvantages including the inconvenience of the delivery, distribution and metabolic process of the photothermal agent and the inaccurate and incomplete evaluation of the results of cancer treatment. The researchers have designed a variety of photothermal agents with multimodal imaging capabilities for cancer diagnosis and treatment. These imaging methods include thermal imaging (TI), photoacoustic (PA) imaging, photoluminescence (PL) imaging, magnetic resonance imaging (MRI), X-ray computed tomography (CT) imaging, and positron emission tomography (PET) imaging. And the imaging-guided cancer treatments have improved the accuracy of tumor visual treatments and greatly facilitated the clinical transformation of PTT. At present, the trend of cancer treatment development has gradually changed from monotherapy to combination therapy. Other therapies in combination with PTT include photodynamic therapy (PDT), chemotherapy, immunotherapy, radiotherapy (RT), sonodynamic therapy (SDT), and other PTT-related therapies. These combination therapies overcome tumor heterogeneity and complexity, reversing multidrug resistance, and reduce unnecessary side effects, and can more effectively achieve cancer diagnosis and treatment. This review summarizes the recent advances in multimodal imaging-guided PTT and multitherapies in combination with PTT for cancer diagnosis and treatment. For a single photothermal treatment, it is often difficult for researchers to effectively monitor the delivery, distribution, metabolism, and excretion of photothermal agents, and to accurately and dynamically track and evaluate the real-time therapeutic effects of tumors. Various strategies have been developed to solve the problems of single photothermal therapy. The new nano-platforms based on PTT-based multimodal imaging methods or therapies reviewed in this paper combine cancer diagnosis and treatment, and effectively overcome the shortcomings of single photothermal anti-tumor therapy, which is difficult to visualize tumors and lack of therapeutic efficiency to provide the development of new cancer diagnosis and treatment technologies new opportunities. Whether it is a single photothermal therapy or a combination of photothermal therapy and other methods, there is still a long way to go to study its therapeutic mechanism and further applications. The ultimate goal of these studies is to go to the clinic, cure the tumor, and benefit mankind. It is believed that with the rapid development of nanotechnology and nanomedicine, these problems will be gradually solved, and the photothermal anti-tumor combination therapy based on multimodal imaging will surely make new breakthroughs.

Background: With improved antiretroviral therapy, people living with HIV are aging and non-AIDS-defining cancers have increasing prevalence in this population. Yet, population-based studies demonstrate that people with HIV are less likely to receive cancer treatment, which contributes to lower cancer-specific survival. Past studies have examined cancer disparities at the provider and healthy system levels, but have not explored the drivers of cancer treatment disparities from the patient’s perspective. We aimed to investigate barriers and facilitators of cancer treatment among patients living with HIV, along with perceptions of their cancer diagnosis and treatment, to inform future interventions, reduce disparities, and improve outcomes. Methods: We conducted in-depth interviews with 27 HIV-infected cancer patients to examine perceptions and care engagement in this population. We recruited equal numbers of patients who had (a) past cancer treatment, (b) were currently undergoing cancer treatment, or (c) experienced challenges with receiving or completing cancer treatment. Semi-structured interviews explored multiple topics related to HIV and cancer care, including treatment decision-making, patient-provider interactions, stigma, coping, and barriers to care. Patients were recruited until thematic saturation was reached. Results: Study participants were predominantly male (n=22, 81%) with a median age of 56 years and median annual household income of $24,000. Prevailing themes from the interviews included descriptions of the “devastating” impact of a cancer diagnosis, with a considerable dual burden of pre-existing HIV. Participants noted that having HIV added anxiety about cancer treatment, side effects, and potential treatment interactions. Among those who experienced cancer treatment adherence challenges, barriers included cancer treatment side effects, stigma, transportation difficulties, cost of care, and challenges with coping and mental health. Despite these challenges, participants generally reported having positive healthcare experiences, including compassionate providers, ease of referral, and sound communication. Several participants indicated that their past experiences of coping with HIV had prepared them to accept and address their cancer diagnosis. Conclusions: This is the first qualitative study assessing barriers and facilitators to cancer care among people living with HIV and cancer in the U.S. For many HIV-infected patients, a cancer diagnosis creates substantial added stress to an already challenging social and medical situation. Often, these stressors impact patients’ ability to complete cancer treatment. Resiliency was noted to be a key facilitator, with participants frequently citing family, friends, faith, and the healthcare system as key sources of support. Citation Format: Kelsey L Corrigan, Brandon A Knettel, Noelani Ho, Stuart Carr, Bijal Shah, Joan Cahill, Melissa Watt, Gita Suneja. Cancer care in people with HIV: Identifying adherence challenges to improve outcomes [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A043.

In the past 30 years there has been a significant increase in the number of publications on phospholipid (PL) metabolism, both for the medical purposes of detection and diagnosis of cancer and for the monitoring of the treatment of human cancers. Most of the work has focused on the pathway that produces phosphatidylcholine, the major component of human cell membranes. The trigger for this research was the advent of applications of NMR spectroscopy in vitro and in vivo in the 1980’s and observations that most cancer cells and tumors had significant increases in the water-soluble PL precursors and breakdown products. Increased phosphocholine (PC) has been focused on as a marker for cancer using Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET). MRS is now used clinically to aid in the diagnosis and severity of some brain tumors; and choline PET is used for the diagnosis and staging of recurrent prostate cancer, paid for by medical insurance companies. Another major area of research starting in the 1990’s was the development of specific choline kinase (CK) inhibitors aimed at the isoenzyme CK-a. This isoenzyme is markedly upregulated in cancer cells and unexpectedly was found to have a role in oncogenic transformation independent of its enzyme function.

Cancer is a deadly disease with complex pathophysiological nature and is the leading cause of death worldwide. Traditional diagnosis methods often detect cancer at a considerably critical stage and the conventional methods of treatment like chemotherapy, radiation therapy, targeted therapy, and immunotherapy have several limitations, multidrug resistance, cytotoxicity, and lack of specificity are a few examples. These pose substantial challenge for effective and favourable cancer treatment. The advent of nanotechnology has revolutionized the face of cancer diagnosis and treatment. Nanoparticles, which have a size range of 1–100 nm, are biocompatible and have special optical, magnetic, and electrical capabilities, less toxic, more stable, exhibit permeability and retention effect, and are used for precise targeting. There are several classes of nanoparticles each having their own sets of unique properties. NPs have played an important role in the drug delivery system, overcoming the multi-drug resistance, reducing the side-effects as seen in conventional therapeutic methods and hence able to solve the limitations of conventional methods of diagnosis and treatment. This review discusses the four major classes of nanoparticles (Lipid based NPs, Carbon NPs and Metallic NPs and Polymeric NPs): their discovery and introduction in medical field, unique properties and characteristics, advantages and disadvantages, sub-categories and characteristics of these categories, major area of application in Cancer diagnosis and treatment, and latest methodologies where these are used in cancer treatment.

Sexual dysfunction in women with cancer

Traditional cancer diagnosis has been aided by the application of nanoparticles (NPs), which have made the process easier and faster. NPs possess exceptional properties such as a larger surface area, higher volume proportion, and better targeting capabilities. Additionally, their low toxic effect on healthy cells enhances their bioavailability and t-half by allowing them to functionally penetrate the fenestration of epithelium and tissues. These particles have attracted attention in multidisciplinary areas, making them the most promising materials in many biomedical applications, especially in the treatment and diagnosis of various diseases. Today, many drugs are presented or coated with nanoparticles for the direct targeting of tumors or diseased organs without harming normal tissues/cells. Many types of nanoparticles, such as metallic, magnetic, polymeric, metal oxide, quantum dots, graphene, fullerene, liposomes, carbon nanotubes, and dendrimers, have potential applications in cancer treatment and diagnosis. In many studies, nanoparticles have been reported to show intrinsic anticancer activity due to their antioxidant action and cause an inhibitory effect on the growth of tumors. Moreover, nanoparticles can facilitate the controlled release of drugs and increase drug release efficiency with fewer side effects. Nanomaterials such as microbubbles are used as molecular imaging agents for ultrasound imaging. This review discusses the various types of nanoparticles that are commonly used in cancer diagnosis and treatment.