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Acute portal vein thrombosis (PVT) is a rare disorder defined by the sudden occlusion of the portal vein, which could be partial or complete. Prothrombotic states, inherited or acquired, are thought to be the cause in patients without cirrhosis or malignancy. However, the aetiology of some cases remains idiopathic despite a multidisciplinary diagnostic approach. The initial diagnostic modality to confirm PVT is either contrast-enhanced abdominal (CT) or MRI; as it can identify predisposing factors, and detect evidence of complications. Eliciting the underlying aetiology is critical to guide overall management and prevent future recurrence. The purpose of treatment is to stop thrombus extension and achieve portal vein patency by anticoagulation to optimise outcomes. Herein, we present an unusual case of spontaneous PVT in a young woman. We will also discuss the evaluation of patients without obvious aetiology.

Modulation of proteasome function by pharmacological interventions and molecular biology tools is an active area of research in cancer biology and neurodegenerative diseases. Curcumin (diferuloylmethane) is a naturally occurring polyphenol that affects multiple signaling pathways and known to modulate PKC activities. The therapeutic significance of curcumin is often considered to reside in its anti-inflammatory, antioxidant, anti-angiogenic, or anti-apoptotic properties. However, recent research suggests that the therapeutic efficacy of curcumin may be due to its activity as a potent inhibitor of the proteasome. In this study, we show that both curcumin and its synthetic polyphenolic derivative (didemethylcurcumin), CUIII modulated proteasome activity in a biphasic manner. Curcumin and CUIII increased proteasome activity at nanomolar concentrations but inhibited proteasome activity at micromolar concentrations. Curcumin was more effective than CUIII in relative proteasome activity increase at nanomolar concentrations. Also, curcumin was more effective than CUIII in relative proteasome activity inhibition at micromolar concentration. The docking study was conducted on the 20S proteasome catalytic subunit. Estimated Kd values for curcumin and didemethylcurcumin are 0.0054μM and 1.3167μM, respectively. These values correlate well with the results of the effectiveness of modulation by curcumin compare to CUIII. The small size of CUIII makes its dock to the narrow cavity of the active site, but the binding interaction is not strong compare to curcumin. This study suggests that curcumin and its didemethyl derivative can be used to modulate proteasome activity. This communication implicates the reason why curcumin and its didemethyl derivative can be used to two different disease mechanisms, neurodegeneration, and cancer.

Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are conditions related to renal failure that can rarely occur in association as a contiguous gene syndrome. Angiomyolipomas (AMLs) are renal tumors strongly related to TSC that may rupture and cause life-threatening bleedings. We present a patient with TSC, ADPKD, and renal AMLs with persistent hematuria requiring blood transfusion. The persistent hematuria was successfully treated through endovascular embolization, a minimally invasive nephron sparing technique. Keywords: Tuberous Sclerosis; Polycystic [...]

Background Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and poor prognosis. miR-637 has been reported to regulate tumor progression and act as a prognosis biomarker of various cancers. Its functional role in NSCLC was investigated in this study. Methods The expression level of miR-637 in NSCLC tissues and adjacent normal tissues of 123 NSCLC patients was analyzed by qRT-PCR. The association between miR-637 and clinical pathological features in the prognosis of patients was analyzed. Cell transfection was performed to overexpress or knockdown miR-637 in H1299 and HCC827. The proliferation, migration, and invasion of H1299 and HCC827 were evaluated by CCK8 and Transwell assay. Results miR-637 expression was significantly decreased in NSCLC tissues and cell lines relative to normal tissues and cells. The survival rate of NSCLC patients with low miR-637 expression was lower than that of patients with high miR-637 expression. Additionally, miR-637 served as a tumor suppressor that inhibited cell proliferation, migration, and invasion of NSCLC. Conclusion Downregulation of miR-637 in NSCLC was associated with TNM stage and poor prognosis of patients and served as a tumor suppressor in NSCLC. These results provide a potential strategy to control NSCLC.

Background: In the recent years, Micelles represent a promising carrier for the treatment and diagnosis of cancer. Architecturally, micelles are self-assembled nanosized colloidal aggregates prepared from amphiphilic surfactant with a hydrophobic core and hydrophilic shell. Such a composition makes them a potential carrier for delivery of hydrophobic anticancer drugs with in their core. Description: Micelles have received increasing interest as an enhanced permeability and retention (EPR) targeted drug delivery systems for cancer treatment. Micelles can be modified to contribute various attractive properties, for instance, active targeting, stimuli-responsiveness. They have also proven their ability in drug targeting to tumor tissue, enhanced drug accumulation, drug stabilization, tissue penetration, prolong circulation, in vivo biocompatibility, biodegradability and reduced side effects. Micelles have displayed a vital role in multidrug delivery for cancer therapy. Results and Discussion : The aim of the present review is to provide an overview on the status of micellar nanoformulations for anticancer agents, including their pre-clinical and clinical researches. Emphasis is placed on presenting the newer strategies to enhance the therapeutic efficacy of anticancer drug at the target site. The type of co-polymers used and methods for the preparation of micelles are also highlighted in the paper.

Colorectal cancer (CRC) is one of the most common cancers worldwide. In this study, we explored the role of RNA binding motif protein 15 (RBM15)-mediated MyD88 mRNA N6-methyladenosine (m6A) in CRC development. Cell proliferation, apoptosis, and invasion were detected by EdU, Annexin V-FITC/PI staining, and Transwell assays, respectively. RBM15 and MyD88 expression was detected by RT-qPCR and Western blot. RNA-seq, RIP-seq, and MeRIP-seq were used for RBM15 downstream target gene prediction and expression detection. In this research, we confirmed that RBM15 was highly expressed in CRC tissues and was negatively correlated with overall and disease-free survival rate. Silencing RBM15 significantly inhibited the proliferative and invasive abilities and promoted cell apoptosis in the CRC cell lines (SW480 and HCT116). Moreover, tumor growth and CRC liver metastasis were inhibited by silencing RBM15 in vivo. m6A methylation level was decreased in RBM15-silenced SW480 and HCT116 cells. MyD88 was the target mRNA of RBM15-mediated m6A methylation in CRC. MyD88 was lowly expressed in CRC and negatively correlated with RBM15 expression. Taken together, RBM15 silencing inhibited the CRC growth and metastasis in vitro and in vivo. RBM15 mediated m6A methylation modification of MyD88 mRNA in CRC cells.

The role of human microbiota in cancer initiation and progression is recognized in recent years. In order to investigate the interactions between cancer cells and microbes, a systematic analysis using various emerging techniques is required. Owing to the label-free, non-invasive and molecular fingerprinting characteristics, vibrational spectroscopy is uniquely suited to decode and understand the relationship and interactions between cancer and the microbiota at the molecular level. In this review, we first provide a quick overview of the fundamentals of vibrational spectroscopic techniques, namely Raman and infrared spectroscopy. Next, we discuss the emerging evidence underscoring utilities of these spectroscopic techniques to study cancer or microbes separately, and share our perspective on how vibrational spectroscopy can be employed at the intersection of the two fields. Finally, we envision the potential opportunities in exploiting vibrational spectroscopy not only in basic cancer-microbiome research but also in its clinical translation, and discuss the challenges in the bench to bedside translation.

Background/Aims: We aimed to estimate the prevalence of comorbidities and medication use in Korean women with rheumatic diseases (RDs) during their childbearing years.Methods: We included women aged 20 to 44 years with seropositive rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) (n = 41,547) and age-matched women without seropositive RA, SLE, and AS (n = 208,941) from the National Health Insurance Service-National Health Information Database (2009 to 2016). The prevalence of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), and cancer and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CSs), and disease-modifying anti-rheumatic drugs (DMARDs) were estimated.Results: Women of childbearing age with RDs were more likely to have at least one of the measured comorbidities than the controls (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.9 to 3.1). The OR (95% CI) was 2.9 (2.8 to 3.0) for HTN, 2.8 (2.7 to 2.9) for HLD, 1.4 (1.4 to 1.5) for DM, and 1.3 (1.3 to 1.4) for cancer. The SLE group had the highest prevalence and odds of all four measured comorbidities. Almost all (97.9%) women of childbearing age with RDs were taking RD-related medications (NSAIDs, 81.6%; CSs, 77.8%; DMARDs, 87.3%). The RD group was 13.8 times more likely to take NSAIDs and 68.2 times more likely to take CSs than the controls. Use of NSAIDs was more prevalent in RA and AS than SLE, whereas use of CSs and DMARDs was more prevalent in RA and SLE than AS.Conclusions: Korean women with RDs have a greater burden of comorbidities and medication use during their childbearing years than women without RDs of the same age.

Cancer is known as one of the leading causes of morbidity and fatality, currently faced by our society. The prevalence of cancer related dieses is rapidly increasing around the world. To reduce the mortality rates, early diagnosis and subsequent treatment of cancer in timely manner is quite essential. Advancements have been made to achieve effective theranostics strategies to tackle cancerous dieses, yet very challenging to overcome this issue. Recently, advances made in the field of nanotechnology have shown tremendous potential for cancer theranostics. Different types of nanomaterials have been successfully employed to develop sophisticated diagnosis and therapy techniques. In this context, graphene and its derivatives e.g. graphene oxide (GO) and reduced graphene oxide (RGO) have been investigated as promising candidates to design graphene-based nanosystems for the diagnosis and therapeutic purpose. Further, to synthesize graphene and its derivatives different types of physicochemical methods are being adopted. However, each method has its own advantage and disadvantages. In this reference, among diverse biological methods, microbial technique can be one of the most promising and eco-friendly approach for the preparation of graphene and its derivatives, particularly GO and RGO. In this review, we summarize studies performed on the preparation of graphene and its derivatives following microbial routes meanwhile focus has been made on the preparation method and the possible mechanism involved therein. Thereafter, we have discussed applications of graphene and its derivatives to developed advanced nanosystem that can be imperative for the cancer theranostics. Results of recent studies exploring applications graphene based nanosystem for the preparation of different types of biosensors for early diagnosis; advanced therapeutic approaches by designing drug delivery nanosystems along with multifunctionality (e.g cancer imaging, drug delivery, photodynamic and photo thermal therapy) in cancer theranostics have been discussed. Particularly, emphasis has been given on the preparation techniques of graphene based nanosystems, being employed in designing of biosensing platforms, drug delivery and multifunctional nanosystems. Moreover, issues have been discussed on the preparation of graphene and its derivatives following microbial technique and the implementation of graphene based nanosystems in cancer theranostics.

Sarcopenia is the loss of muscle mass and function related to aging, undereating, disease conditions, or inactivity. Pre-existing sarcopenia diminishes the functional reserve of patients with cancer which increases their risk for frailty, cancer cachexia, and worse outcomes from treatments. The pathogenesis of sarcopenia is multi-factorial: opening opportunities for clinicians to work across disciplines to improve patient outcomes and quality of life. The purpose of this essay is to describe sarcopenia, discuss clinical screening and assessment for sarcopenia, and highlight potential interventions to manage sarcopenia in the urologic oncology population.

The active role of bacteria in oncogenesis has long been a topic of debate. Although, it was speculated to be a transmissible cause of cancer as early as the 16th-century, yet the idea about the direct involvement of bacteria in cancer development has only been explored in recent decades. More recently, several studies have uncovered the mechanisms behind the carcinogenic potential of bacteria which are inflammation, immune evasion, pro-carcinogenic metabolite production, DNA damage and genomic instability. On the other side, the recent development on the understanding of tumor microenvironment and technological advancements has turned this enemy into an ally. Studies using bacteria for cancer treatment and detection have shown noticeable effects. Therapeutic abilities of bioengineered live bacteria such as high specificity, selective cytotoxicity to cancer cells, responsiveness to external signals and control after ingestion have helped to overcome the challenges faced by conventional cancer therapies and highlighted the bacterial based therapy as an ideal approach for cancer treatment. In this review, we have made an effort to compile substantial evidence to support the multidimensional role of bacteria in cancer. We have discussed the multifaceted role of bacteria in cancer by highlighting the wide impact of bacteria on different cancer types, their mechanisms of actions in inducing carcinogenicity, followed by the diagnostic and therapeutic potential of bacteria in cancers. Moreover, we have also highlighted the existing gaps in the knowledge of the association between bacteria and cancer as well as the limitation and advantage of bacteria-based therapies in cancer. A better understanding of these multidimensional roles of bacteria in cancer can open up the new doorways to develop early detection strategies, prevent cancer, and develop therapeutic tactics to cure this devastating disease.

Advances in the development of anti-tumour drugs and related technologies have resulted in a significant increase in the number of cancer survivors. However, the incidence of chemotherapy-induced cardiotoxicity (CIC) has been rising continuously, threatening their long-term survival. The integration of nanotechnology and biomedicine has brought about an unprecedented technological revolution and has promoted the progress of anti-tumour therapy. In this review, we summarised the possible mechanisms of CIC, evaluated the role of nanoparticles (including liposomes, polymeric micelles, dendrimers, and hydrogels) as drug carriers in preventing cardiotoxicity and proposed five advantages of nanotechnology in reducing cardiotoxicity: Liposomes cannot easily penetrate the heart's endothelial barrier; optimized delivery strategies reduce distribution in important organs, such as the heart; targeting the tumour microenvironment and niche; stimulus-responsive polymer nano-drug carriers rapidly iterate; better economic benefits were obtained. Nanoparticles can effectively deliver chemotherapeutic drugs to tumour tissues, while reducing the toxicity to heart tissues, and break through the dilemma of existing chemotherapy to a certain extent. It is important to explore the interactions between the physicochemical properties of nanoparticles and optimize the highly specific tumour targeting strategy in the future.

When treating cancer patients, the progression of symptoms is accompanied by the deterioration of systemic conditions and motor function. From a risk-benefit perspective, a certain level of physical function must be maintained to continue cancer treatment. Recently, outpatient cancer treatment has become more common. Motor function is important to determine the feasibility of continuing cancer treatment. The study aimed to evaluate the motor function of patients with visceral cancer using locomo tests established by Japanese Orthopaedic Association.Locomo tests were performed, and the results were compared with data from non-cancer individuals. Background data were matched by propensity score matching. Data from 53 cancer patients (group C) were compared with that of 75 non-cancer patients (group N).The average score in the two-step test of group C was lower than that of group N (1.27: 1.37, p = 0.004). The average function in the stand-up test of group C was worse than that of group N (p = 0.001). The average score in the 25-question geriatric locomotive function scale (GLFS) of group C was significantly higher than that of group N (19.92: 5.29, SE 2.21, p 0.001). Higher 25-question GLFS scores indicate reduced mobility. The proportion of the locomo stage 2 in group C was significantly higher than in group N (51%: 13%, p 0.001). The results of the two field tests revealed a clinically minimal difference between the two groups, but a statistically significant difference. Locomo tests may be detect potential motor dysfunction in outpatient cancer patients with apparently maintained motor function.Even in cancer patients who attend outpatient clinics, their motor functions could be potentially impaired. Therapeutic interventions to maintain and enhance motor function for cancer patients could be useful for continuing cancer treatment, and furthermore, improving prognosis.

Patients after heart transplantation are at increased risk for malignancy secondary to immunosuppression and oncogenic viral infections. Most common among children is posttransplant lymphoproliferative disorder (PTLD), occurring in 5% to 10% of patients. We used a national database to examine the incidence and risk factors for posttransplant malignancy.The United Network for Organ Sharing database was queried for pediatric (18 years) heart transplant recipients from October 1987 through November 2019. Freedom from malignancy after transplant was assessed with Kaplan-Meier analysis. Cox regression was performed to generate hazard ratios (HRs) and 95% CIs for risk of malignancy development.Of 8581 pediatric heart transplant recipients, malignancy developed in 8.1% over median follow-up time of 6.3 years, with PTLD compromising 86.4% of the diagnosed cancers. The incidence of PTLD development was 1.3% at 1 year and 4.5% at 5 years. Older age at the time of transplant was protective against the development of malignancy (HR, 0.98; 95% CI, 0.96-0.99; P.001), whereas a history of previous malignancy (HR, 1.9; 95% CI, 1.2-3.0; P = .007) and Ebstein-Barr virus (EBV) recipient-donor mismatch (HR, 1.7; 95% CI, 1.3-2.2; P.001) increased the risk. Induction therapy, used in 78.9% of the cohort, did not increase malignancy risk (P = .355) nor did use of maintenance tacrolimus (P = .912).PTLD occurred after 7% of pediatric heart transplants, with risk increased by younger age and EBV mismatch, highlighting the importance of PTLD monitoring in EBV-seronegative recipients. Induction therapy, used in most of the pediatric heart transplants, does not seem to increase posttransplant malignancy nor does tacrolimus, the most commonly used calcineurin inhibitor.

The intentional use of viruses for cancer therapy dates back over a century. As viruses are inherently immunogenic and naturally optimized delivery vehicles, repurposing viruses for drug delivery, tumor antigen presentation, or selective replication in cancer cells represents a simple and elegant approach to cancer treatment. While early virotherapy was fraught with harsh side effects and low response rates, virus-based therapies have recently seen a resurgence due to newfound abilities to engineer and tune oncolytic viruses, virus-like particles, and virus-mimicking nanoparticles for improved safety and efficacy. However, despite their great potential, very few virus-based therapies have made it through clinical trials. In this review, we present an overview of virus-inspired approaches for cancer therapy, discuss engineering strategies to enhance their mechanisms of action, and highlight their application for overcoming the challenges of traditional cancer therapies.

In cancer, human cells lose the ability to properly control the series of events that occur constantly during cell growth and division, including protein expression, stability, and dynamics. Heat shock proteins (Hsps) are key molecules in these events, constitutively expressed at high levels and could furthermore be induced by the response to cancer-induced stress. In tumor cells, Hsps have been shown to be implicated in the regulation of apoptosis, immune responses, angiogenesis and metastasis; in some cases, they can be overexpressed and dysregulated, representing important cancer hallmarks. In the past few years, it has been demonstrated that Hsps can be released by tumor cells through several secreting pathways, including the extracellular vesicles (EVs), thus modulating the tumor microenvironment as well as long-distance intercellular communication and metastatization. In this review, we discuss the role of extracellular Hsps in cancer, with a particular interest in Hsps in EVs. We would also like to highlight the importance of fully understanding of the role of extracellular Hsps released by EVs and encourage further research in this field the use of Hsps as early cancer biomarkers and therapeutic targets.

Objectives To evaluate the ability of an artificial intelligence (AI) model to predict the risk of cancer in patients referred from primary care based on routine blood tests. Results obtained with the AI model are compared to results based on logistic regression (LR). Methods An analytical profile consisting of 25 predefined routine laboratory blood tests was introduced to general practitioners (GPs) to be used for patients with non-specific symptoms, as an additional tool to identify individuals at increased risk of cancer. Consecutive analytical profiles ordered by GPs from November 29th 2011 until March 1st 2020 were included. AI and LR analysis were performed on data from 6,592 analytical profiles for their ability to detect cancer. Cohort I for model development included 5,224 analytical profiles ordered by GP’s from November 29th 2011 until the December 31st 2018, while 1,368 analytical profiles included from January 1st 2019 until March 1st 2020 constituted the “out of time” validation test Cohort II. The main outcome measure was a cancer diagnosis within 90 days. Results The AI model based on routine laboratory blood tests can provide an easy-to use risk score to predict cancer within 90 days. Results obtained with the AI model were comparable to results from the LR model. In the internal validation Cohort IB, the AI model provided slightly better results than the LR analysis both in terms of the area under the receiver operating characteristics curve (AUC) and PPV, sensitivity/specificity while in the “out of time” validation test Cohort II, the obtained results were comparable. Conclusions The AI risk score may be a valuable tool in the clinical decision-making. The score should be further validated to determine its applicability in other populations.

Organoid (hypermature) teratomas are highly specialized teratomas showing organ formation, most frequently from the digestive tract or bronchial wall. We present four cases of ovarian organoid teratomas, one with a distinguishable mandible with teeth, one with small intestine, one with large intestine containing a well differentiated neuroendocrine tumor and another with both large intestine and bronchial wall. These tumors have a distribution similar to conventional teratomas and usually behave benignly, although cases of malignancy have been reported.

Abstract: Cancer is an important health issue worldwide. Cancer therapy is multifaceted, and drug resistance is still the major limiting factor in the treatment of patients with this disease. Although the mechanisms of anticancer drug resistance have been broadly investigated, a massive biological signal pathway of Non-coding RNAs (ncRNAs) involved in this process has not been completely understood. Long noncoding RNAs (lncRNAs) are a kind of transcripts with a minimum length of 200 nucleotides in size, which have a limited potential for coding proteins. The roles of these RNA molecules have been evaluated in relation to several pathological processes, including tumor formation and progression. Increasing evidence has recently reported that non-coding RNAs (ncRNAs), particularly long non-coding RNAs, have significant roles in many cellular and genomic processes, and because of their potential in regulation specific genes, they are also involved in drug resistance. In this review, we review the literature on the features of lncRNA, their regulation roles in the gene expression related to chemo resistance, and the potential of these RNAs as targeted therapies for personalized treatment in cancers.

Accumulating evidence has demonstrated that cancer stem cells (CSCs) play an essential role in tumor progression and reoccurrence and drug resistance. Multiple signaling pathways have been revealed to be critically participated in CSC development and maintenance. Emerging evidence indicates that numerous chemopreventive compounds, also known as nutraceuticals, could eliminate CSCs in part via regulating several signaling pathways. Therefore, in this review, we will describe the some natural chemopreventive agents that target CSCs in a variety of human malignancies, including soy isoflavone, curcumin, resveratrol, tea polyphenols, sulforaphane, quercetin, indole-3-carbinol, 3,3'-diindolylmethane, withaferin A, apigenin, etc. Moreover, we discuss that eliminating CSCs by nutraceuticals might be a promising strategy for treating human cancer via overcoming drug resistance and reducing tumor reoccurrence.

The RAF-MEK-ERK signaling cascade is a well-characterized MAPK pathway involved in cell proliferation and survival. The three-layered MAPK signaling cascade is initiated upon RTK and RAS activation. Three RAF isoforms ARAF, BRAF and CRAF, and their downstream MEK1/2 and ERK1/2 kinases constitute a coherently orchestrated signaling module that directs a range of physiological functions. Genetic alterations in this pathway are among the most prevalent in human cancers, which consist of numerous hot-spot mutations such as BRAFV600E. Oncogenic mutations in this pathway often override otherwise tightly regulated checkpoints to open the door for uncontrolled cell growth and neoplasia. The crosstalk between the RAF-MEK-ERK axis and other signaling pathways further extends the proliferative potential of this pathway in human cancers. In this review, we summarize the molecular architecture and physiological functions of the RAF-MEK-ERK pathway with emphasis on its dysregulations in human cancers, as well as the efforts made to target the RAF-MEK-ERK module using small molecule inhibitors.

Background: Some reports have described intraosseous arteriovenous fistulas showing osteolytic changes, but an osseous arteriovenous fistula (AVF) at the jugular bulb showing extensive bone destruction is a very rare disease. Case description: A 60-year-old man presented with pulsatile tinnitus and right facial nerve palsy. Radiological imaging showed a large homogenously enhanced osteolytic lesion at the right jugular foramen. A cerebral angiogram showed a high-flow vascular lesion of the jugular bulb associated with retrograde sinus reflux, resulting in venous congestion of the deep venous system. These findings led us to misdiagnose this lesion as a glomus jugular tumor. However, combined arterial and venous angiography after transarterial embolization revealed the precise angioarchitecture, and we finally diagnosed this lesion as a high-flow osseous AVF at the jugular bulb. We performed transvenous embolization using a triple catheter technique. The lesion was successfully obliterated, and the 6-months angiogram showed no recurrence. Conclusion: A rare case of high flow osseous AVF at the jugular bulb associated with osteolytic changes in the surrounding bony structure is reported. Although many hypervascular lesions at the jugular bulb are glomus tumors, bone destructive osseous AVF at the jugular bulb should be considered.

Background: Cancer, a malignant tumor, is caused by the failure of the mechanism that controls cell growth and proliferation. Late clinical symptoms often manifest as lumps, pain, ulcers, and bleeding. Systemic symptoms include weight loss, fatigue, and loss of appetite. It is a major disease that threatens human life and health. How to treat cancer is a long-standing problem that needs to be overcome in the history of medicine. Discussion: In this study, we systematically review the cancer treatment evolution from traditional methods to novel approaches that include immunotherapy, nanotherapy, stem cell theapy, and gene therapy. We provide the latest review of the application status, clinical trials, and development prospects of mesenchymal stem cells and gene therapy for cancer, as well as their integration in cancer treatment. Mesenchymal stem cells are effective carriers carrying genes and provide new clinical ideas for tumor treatment. Methods: Traditional tumor treatment methods are poorly targeted, and the side effects of treatment seriously damage the physical and mental health of patients. In recent years, with the advancement of medical science and technology, the research on gene combined with mesenchymal stem cells to treat tumors has been intensified. Mesenchymal stem cells carry genes to target cancer cells, which can achieve better therapeutic effects. Conclusion: This review focuses on the current status, application prospects, and challenges of mesenchymal stem cell combined gene therapy for cancer and provides new ideas for clinical research.

The Surveillance, Epidemiology and End Results (SEER) and the National Cancer Database (NCDB) are databases for cancer analysis that may be subject to error in data reporting. This study examined the rates and impact of discordant data for non-small cell lung cancer.NCDB and SEER were queried for non-small cell lung cancer pathologic tumor, node, metastasis data (NCDB) or "derived" data (SEER). Discordancy between descriptors with stage and impact of outlier data were analyzed.Incomplete staging was noted in 71.5% of the NCDB and 10.3% of SEER patients. A total of 174 829 patients from the NCDB and 117 114 from SEER were analyzed. The NCDB had 97 cases with ≥20 positive lymph nodes recorded vs 27 in SEER (P.001). Mean and median sampled lymph nodes were skewed with inclusion of these data points (P .001). The NCDB misclassified 0.99% tumors5 cm as stage I vs 0.04% in SEER (P.001). The NCDB misstaged positive lymph nodes as pathologic N0 (0.59%) or stage 0 or stage I (0.65%). The NCDB misclassified pathologic N1 as lower than stage II (0.91%) or N2 as lower than stage III (0.36%). The NCDB misclassified stage I with documentation of pathologic N1 or N3 disease (0.24%) or stage II with evidence of N2 or N3 disease (0.50%). The NCDB misclassified pathologic M1 as pathologic stageIV in 0.9% of cases and misclassified 19.8% of stage IV as pathologic M0. SEER collaborative staging had no discordance (P.001).The NCDB and SEER are 2 powerful cancer databases. However, the cumulative discordancy rate was 4.9% for the NCDB and 0.008% for SEER, with more misstaging and outliers in the NCDB.

Cancer is characterized by an extremely complex biological background, which hinders personalized therapeutic interventions. Precision medicine promises to overcome this obstacle through integrating information from different ‘subsystems’, including the host, the external environment, the tumor itself and the tumor micro-environment. Immunogenetics is an essential tool that allows dissecting both lymphoid cancer ontogeny at both a cell-intrinsic and a cell-extrinsic level, i.e. through characterizing micro-environmental interactions, with a view to precision medicine. This is particularly thanks to the introduction of powerful, high-throughput approaches i.e. next generation sequencing, which allow the comprehensive characterization of immune repertoires. Indeed, NGS immunogenetic analysis (Immune-seq) has emerged as key to both understanding cancer pathogenesis and improving the accuracy of clinical decision making in oncology. Immune-seq has applications in lymphoid malignancies, assisting in the diagnosis e.g. through differentiating from reactive conditions, as well as in disease monitoring through accurate assessment of minimal residual disease. Moreover, Immune-seq facilitates the study of T cell receptor clonal dynamics in critical clinical contexts, including transplantation as well as innovative immunotherapy for solid cancers. The clinical utility of Immune-seq represents the focus of the present contribution, where we highlight what can be achieved but also what must be addressed in order to maximally realize the promise of Immune-seq in precision medicine in cancer.

This study examined the joint associations of sleep patterns and physical activity (PA) with all-cause, cardiovascular disease (CVD), and cancer mortality.A total of 341,248 adults (mean age = 39.7 years; men: 48.3%) were included in the study, with a 15-year follow-up. Participants reported sleep duration and disturbances (difficulty falling asleep, easily awakened, or use of sleeping medication). PA was classified into 4 levels:7.5, 7.5-14.9, 15.0-29.9, and ≥30.0 metabolic equivalent hours per week (MET-h/week). To understand the joint associations of sleep patterns and PA with mortality, Cox proportional hazard models were conducted, with exposure variables combining sleep duration/disturbances and PA.Compared with the reference group (sleeping 6-8 h/day), individuals who slept8 h/day had higher risk for all-cause mortality (hazard ratio (HR) = 1.307, 95% confidence interval (95%CI): 1.248-1.369), CVD mortality (HR = 1.298, 95%CI: 1.165-1.445), and cancer mortality (HR = 1.128, 95%CI: 1.042-1.220). Short sleep duration was not associated with mortality risk. Increased risk of all-cause and CVD mortality was found in participants who had difficulty falling asleep (HR = 1.120, 95%CI: 1.068-1.175; HR = 1.163, 95%CI: 1.038-1.304, respectively), and used sleeping medication (HR = 1.261, 95%CI: 1.159-1.372; HR = 1.335, 95%CI: 1.102-1.618, respectively) compared with those who slept well. Long sleep duration and sleep disturbances were not associated with risk of all-cause and CVD mortality among individuals achieving a PA level of ≥15 MET-h/week, and in particular among those achieving ≥30 MET-h/week.Long sleep duration, difficulty falling asleep, and use of sleeping medication were related to a higher risk of death. Being physically active at a moderate intensity for 25-65 min/day eliminated these detrimental associations.

Cancer Biomarkers are the key to unlocking the promise of precision oncology, selecting which patients will respond to a more personalised treatment while sparing non-responders the therapy-related toxicity. In this paper, we highlight the primacy of cancer biomarkers, but focus on their importance to patients and to health systems. We also highlight how cancer biomarkers represent value for money. We emphasise the need for cancer biomarkers infrastructure to be embedded into European health systems. We also highlight the need to deploy multiple biomarker testing to deliver the optimal benefit for patients and health systems and consider cancer biomarkers from the perspective of cost, value and regulation. Cancer biomarkers must also be situated in the context of the upcoming In Vitro Diagnostics Regulation, which may pose certain challenges (e.g. non-compliance of laboratory developed tests, leading to cancer biomarker shortages and increased costs) that need to be overcome. Cancer biomarkers must be embedded in the real world of oncology delivery and testing must be implemented across Europe, with the intended aim of narrowing, not widening the inequity gap for patients. Cancer patients must be placed firmly at the centre of a cancer biomarker informed precision oncology care agenda.

Background Cancer risk is determined by specific factors, including body weight and dietary patterns. Accordingly, the World Cancer Research Fund/American Institute for Cancer Research published updated cancer prevention recommendations in 2018 based on comprehensive reviews of modifiable behaviors associated with cancer risk. Objective The objective of this study was to determine the extent to which US adults meet these evidence-based recommendations and how adherence differs by weight status. Design This was a cross-sectional study using nationally representative data from the 2005-2016 National Health and Nutrition Examination Survey (NHANES). Participants/setting Dietary intake data for 30,888 adults 18 years and older with normal body mass index (BMI), overweight, or obesity were analyzed. Main outcome measures Differences in dietary intakes and the proportion of adults meeting guidelines were compared across BMI categories. Statistical analyses performed Logistic regression and 1-way analysis of covariance were used to analyze differences in adherence to recommendations, controlling for age, sex, race/ethnicity, and family income as a percent of the federal poverty rate. Results Regarding fruit and nonstarchy vegetables, 62.8% of adults with normal BMI, 64.5% with overweight, and 70.1% with obesity fell short of recommendations. Regarding whole grains, 67.9% of adults with normal BMI, 70.2% with overweight, and 73.1% with obesity did not meet the recommendation. Regarding red meat, 36.7% of adults with normal BMI, 41.6% with overweight, and 43.5% with obesity consumed >18 oz/week, with a significant difference in mean intakes between adults with normal BMI and obesity (P Conclusions Few U.S. adults meet cancer prevention recommendations; adults with obesity are significantly less likely to do so. Future research should evaluate compounded risk resulting from obesity and poor dietary patterns inconsistent with current evidence-based guidelines, and inform targeted interventions to address these issues.

BRAF-inhibitors have emerged as a promising targeted therapy for malignancies with BRAF mutations, particularly metastatic melanoma. However, granulomatous reactions including sarcoidosis and sarcoid-like-reactions have been reported as a consequence of BRAF-inhibition. It is important to adequately characterise these granulomatous reactions including cutaneous manifestations and systemic involvement, in order to guide investigations and management. A literature review was conducted to characterise the spectrum of granulomatous reactions associated with BRAF-inhibitors - identifying 55 reactions affecting 51 patients, with 37 reactions limited to cutaneous involvement. Further, possible correlation with cancer response, mechanisms of granuloma formation, as well as a proposed workup and management approach for these granulomatous reactions are presented.

Genomic profiling technologies have enabled the development of targeted therapies designed to target specific biomarkers and molecular pathways involved in the pathophysiology of tumor initiation, metastasis, and drug resistance. In recent years, clinical trials with innovative design focus on the development of novel agents based on specific patient molecular alterations or other tumor characteristics and include patients with heterogenous tumor types. Precision oncology studies with innovative design associated with novel dose-finding approaches and data analysis focusing on subgroups of patients are characteristic of master protocols. Real-world data, patient-reported outcomes, and N-of-1 trials enhance the knowledge base of evidence to deliver personalized treatment to patients. Master protocols accelerate drug development by enabling simultaneous multiple sub-studies that match the patient's tumor molecular profile with experimental treatment arms. However, the increased flexibility of precision oncology trials is often associated with small subpopulations of patients, which may be underpowered to draw statistically robust conclusions. Despite their limitations, innovative clinical trials continue to rapidly translate the emerging discoveries of novel drugs into unprecedented clinical outcomes in patients with cancer and to accelerate the implementation of precision oncology.

BackgroundOver the last decades, a decrease in short-term mortality in cancer patients admitted to the ICU has been described in literature. However, it is unclear whether this decrease also results in a decrease in long-term mortality. Therefore, we examined the 1-year mortality of cancer patients (either haematological or solid) with an unplanned ICU admission.Methods and dataAll adult patients registered in the National Intensive Care Evaluation registry with an unplanned ICU admission in the Netherlands between 2008 and 2017 were included. The primary outcome was 1-year mortality, analysed with a mixed-effects cox-proportional hazard regression. We examined the trend in mortality rates over the inclusion period. Furthermore, we compared the 1-year mortality of cancer patients to that of patients without cancer. ResultsWe included 470,305 patients: 10,401 with haematological cancer, 35,920 with solid tumours, and 423,984 without cancer. The 1-year mortality rates were 60.1%, 46.2%, and 28.3% (pConclusionThe 1-year mortality in cancer patients with an unplanned ICU admission (either haematological or solid) was significantly higher than that of patients without cancer. A visual inspection showed a slight decrease in 1-year mortality in haematological patients, while the 1-year mortality in patients with a solid tumour varied per year. After hospital discharge, a considerable part of the patients with a malignancy died within 1 year. Physicians should discuss the long-term prognosis after an ICU admission with patients and relatives in order to manage treatments and expectations. Future research should focus on identifying cancer patients who will benefit from an ICU admission.

Epigenetic patterns in a cell control the expression of genes and consequently determine the phenotype of a cell. Cancer cells possess altered epigenomes which include aberrant patterns of DNA methylation, histone tail modifications, nucleosome positioning and of the three-dimensional chromatin organization within a nucleus. These altered epigenetic patterns are potential useful biomarkers to detect cancer cells and to classify tumor types. In addition, the cancer epigenome dictates the response of a cancer cell to therapeutic intervention and, therefore its knowledge, will allow to predict response to different therapeutic approaches. Here we review the current state-of-the-art technologies that have been developed to decipher epigenetic patterns on the genomic level and discuss how these methods are potentially useful for precision oncology.

Background: Recently, several clinical studies have reported that combination treatments of radiation therapy (RT) and immunotherapy in patients with multiple lesions can improve tumor regression a...

Breast cancer is the second most common cancer type and is the leading cause of cancer-related deaths worldwide. Since it is a heterogeneous disease, subtyping breast cancer plays an important role in performing a specific treatment. Gene expression data is a viable alternative to be employed on cancer subtype classification, as they represent the state of a cell at the molecular level, but generally has a relatively small number of samples compared to a large number of genes. Gene selection is a promising approach that addresses this uneven high-dimensional matrix of genes versus samples and plays an important role in the development of efficient cancer subtype classification. In this work, an innovative outlier-based gene selection (OGS) method is proposed to select relevant genes for efficiently and effectively classify breast cancer subtypes. Experiments show that our strategy presents an F1 score of 1.0 for basal and 0.86 for her 2, the two subtypes with the worst prognoses, respectively. Compared to other methods, our proposed method outperforms in the F1 score using 80% less genes. In general, our method selects only a few highly relevant genes, speeding up the classification, and significantly improving the classifier's performance.

Background: Colorectal cancer (CRC) is a common malignancy of digestive tract. Pinocembrin (PINO) has been discovered to have proapoptotic effect on CRC. This study aimed to elucidate how other biological behaviors of CRC cells were affected under PINO treatment. Materials & Methods: The effect of PINO on HT29 and HCT116 cells were detected through treatment of different concentrations of PINO. The role of LACTB in PINO treatment was investigated by transfection of siRNA-LACTB. Cell counting kit-8 assay, wound healing assay, and Transwell assay were conducted to evaluate the proliferation, migration, and invasiveness of CRC cells, respectively. Western blot or quantitative reverse transcription-polymerase chain reaction was carried out to measure the expressions of LACTB, matrix metalloproteinase (MMP)-2, E-cadherin, and N-cadherin. Results: Gradient PINO inhibited the viability, migration, invasiveness, and expressions of MMP-2 and N-cadherin in CRC cells, while promoted E-cadherin and LACTB expressions. Silencing LACTB promoted the viability, migration, invasiveness, and expressions of MMP-2 and N-cadherin in CRC cells and inhibited E-cadherin expression. PINO counteracted the effect of silenced LACTB, and yet silencing LACTB partially abolished the effect of PINO on CRC cells. Conclusion: PINO inhibited the proliferation, migration, invasiveness, and epithelial-to-mesenchymal transition of CRC cells by regulating LACTB.

Background Peripherally inserted central catheters (PICCs) are commonly used in cancer patients. PICC-associated upper limb venous thromboembolism (PaULVTE, non-deep and deep involving veins proximal to the brachial vein) and distant VTE (i.e. pulmonary embolism [PE], lower limb deep vein thrombosis [DVT]) prevention is important due to the bleeding risk from subsequent anticoagulation. The Khorana risk score (KRS) is used to predict VTE in malignancies, has been externally validated and prospectively utilized in VTE prophylaxis studies in cancer patients. It utilizes routinely available variables: cancer type, prechemotherapy platelet count, hemoglobin, leukocyte count and body mass index (BMI) to stratify patients into three risk groups. However, the KRS was not designed to predict PaULVTE so its utility in this context is unknown. A specific PaULVTE risk model is the Michigan Risk Score (MRS) which assesses concurrent central catheter at time of PICC insertion, leukocyte count at insertion, PICC lumen number, antecedent VTE (DVT or PE) and active cancer (the latter confers a score of 3). The MRS has not been externally validated and is not specifically designed for cancer patients which comprised 6.2% of their derivation cohort. Objectives To measure the discriminative ability for PaULVTE of the KRS and MRS and the corresponding prevalence of PaULVTE in patients with active cancer in various KRS and MRS strata. To modify the KRS and MRS, to improve discriminative accuracy for PaULVTE. Methods We retrospectively reviewed consecutive patients with malignancies, who received chemotherapy through a PICC between April 2017 to July 2018. Exclusion criteria for cancer cases included PICC insertion for other reasons such as supportive care. We did not exclude patients on prophylactic or therapeutic anticoagulation or those with a history of PaULVTE. The outcome measures included objectively confirmed PaULVTE incidence whilst the PICC remained in place or within 30 days post removal, treatment and to assess the prevalence of PaULVTE according to KRS and MRS categories in patients with active cancer. For cancer patients, KRS and MRS were calculated based on clinical and laboratory values at PICC insertion. We also assessed whether combining components of both scores would yield improved discriminative ability. Furthermore, we recorded symptomatic, radiologically confirmed distant VTE (i.e. PE, DVT in the proximal or distal lower limb) if this occurred whilst the PICC was in situ or up to 30 days post removal. Results Among 147 cancer patients, median age 64 years, PICC duration 70 days (range, 2-452), 7% developed PaULVTE (95%CI 3.6-12.2) and 4%(95%CI 2-9) distant VTE. Of KRS3, p=0.01 (Figure 2). The addition of lumen number from MRS to KRS did not improve the area under the curve (0.6 [95%CI 0.44-0.82]). Conclusion PaULVTE risk is high in active cancer (7%). The MRS dichotomized at a score of above or less than 5 showed moderate discriminative ability for PaULVTE. With simple modification of the MRS with the addition of thrombocytosis (mMRS), a score of 3 had a low rate of PaULVTE (1.4%) and accounted for 47% of patients. mMRS>3 comprised 53% of the cohort and had a statically higher rate of PaULVTE 11.8%. More patients were accurately classified as low PaULVTE risk using mMRS3 compared to KRS Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

ObjectivePsycho-oncological institutions offer specialized care for cancer patients. Little is known how this care might impact fatigue. This study aimed to identify fatigue trajectories during psychological care, examined factors distinguishing these trajectories and predicted fatigue severity after nine months of psychological care.DesignNaturalistic, longitudinal study of 238 cancer patients receiving psycho-oncological care in the Netherlands. Data were collected before initiation of psychological care (T1) and three (T2) and nine months (T3) afterwards. Latent class growth analysis, repeated measure analyses (RMA) and linear regression analysis were performed.Main Outcome MeasuresFatigue severity: Checklist Individual Strength.ResultsThree fatigue trajectories were identified: high- (30%), moderate- (62%) and low-level fatigue (8%). While statistically significant decreases in fatigue were found, this decrease was not clinically relevant. RMA showed main effects for time for fatigue trajectories on depression, anxiety, personal control and illness cognitions. Fatigue severity and physical symptoms at T1, but not demographic or clinical factors, were predictive of fatigue severity at T3.ConclusionsFatigue is very common during psycho-oncological care, and notably not clinically improving. As symptoms of fatigue, depression, anxiety and physical symptoms often cluster, supplementary fatigue treatment should be considered when it is decided to treat other symptoms first.

Somatic mutations accumulating over a patient's lifetime are well-defined causative factors that fuel carcinogenesis. It is now clear, however, that epigenomic signature is also largely perturbed in many malignancies. These alterations support the transcriptional program crucial for the acquisition and maintenance of cancer hallmarks. Epigenetic instability may arise due to the genetic mutations or transcriptional deregulation of the proteins implicated in epigenetic signaling. Moreover, external stimulation and physiological aging may also participate in this phenomenon. The epigenomic signature is frequently associated with a cell of origin, as well as with tumor stage and differentiation, which all reflect its high heterogeneity across and within various tumors. Here, we will overview the current understanding of the causes and effects of the altered and heterogeneous epigenomic landscape in cancer. We will focus mainly on DNA methylation and post-translational histone modifications as the key regulatory epigenetic signaling marks. In addition, we will describe how this knowledge is translated into the clinic. We will particularly concentrate on the applicability of epigenetic alterations as biomarkers for improved diagnosis, prognosis, and prediction. Finally, we will also review current developments regarding epi-drug usage in clinical and experimental settings.

Interaction of a tumor with its microenvironment is an emerging field of investigation, and the crosstalk between cancer cells and the extracellular matrix is of particular interest, since cancer patients with abundant and stiff extracellular matrices display a poorer prognosis. At the post-juvenile stage, the extracellular matrix plays predominantly a structural role by providing support to cells and tissues; however, during development, matrix proteins exert a plethora of diverse signals to guide the movement and determine the fate of pluripotent cells. Taking a closer look at the communication between the extracellular matrix and cells of a developing body may bring new insights into cancer biology and identify cancer weaknesses. This review discusses parallels between the extracellular matrix roles during development and tumor growth.

Tumour-promoting inflammation is a critical hallmark in cancer development, and inflammasomes are well-known regulators of inflammatory processes within the tumour microenvironment. Different inflammasome components along with the adaptor, apoptosis-associated speck-like protein containing caspase activation and recruitment domain (ASC), and the effector, caspase-1, have a significant influence on tumorigenesis but in a tissue-specific and stage-dependent manner. The downstream products of inflammasome activation, that is the proinflammatory cytokines such as IL-1β and IL-18, regulate tissue homeostasis and induce antitumour immune responses, but in contrast, they can also favour cancer growth and proliferation by directing various oncogenic signalling pathways in cancer cells. Moreover, different epigenetic mechanisms, including DNA methylation, histone modification and noncoding RNAs, control inflammasomes and their components by regulating gene expression during cancer progression. Furthermore, autophagy, a master controller of cellular homeostasis, targets inflammasome-induced carcinogenesis by maintaining cellular homeostasis and removing potential cancer risk factors that promote inflammasome activation in support of tumorigenesis. Here, in this review, we summarize the effect of inflammasome activation in cancers and discuss the role of epigenetic and autophagic regulatory mechanisms in controlling inflammasomes. A proper understanding of the interactions among these key processes will be useful for developing novel therapeutic regimens for targeting inflammasomes in cancer.

The Notch signaling pathway is an evolutionarily conserved pathway usually present in multicellular organisms, which plays a pivotal role in cell fate determination and proliferation. Due to this property, it is known to be highly oncogenic, especially in the dysregulated version of the Notch pathway, where apoptosis is inhibited and abnormal cell growth is supported. Notch receptors and ligand proteins play an essential role in cancers, such as myeloid leukemia, T-cell lymphoblastic leukemia, and organ-specific, i.e., breast, colon, pancreas, and skin cancers. Any type of cancer generates due to genetic defects, including epigenetic alterations and mutations. The researchers can use these alterations to find a promising diagnostic as well as therapeutic tool for cancer. The successful inhibition of the Notch pathway with the help of specific biomarkers or suppression of gene expression represents a new remedy in cancer research. This article focuses on the various remedies hidden within the Notch pathway's mechanism, primarily based on different patents published in recent years for assisting cancer diagnosis and succeeding treatment.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increasing in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

Background: Cancer pain prevalence remains high, and variance in self-efficacy for managing pain may explain why some patients experience greater pain severity. Aim: This study explored perceptions of self-efficacy in relation to cancer pain severity and treatment related characteristics. Method: A descriptive cross-sectional survey was administered to 50 cancer outpatients. Data analysis involved descriptive and correlational statistical analyses. Results: Self-efficacy to manage pain was significantly associated with time since diagnosis and ability to deal with frustration, and inversely associated with pain severity level. A large proportion of patients reported low satisfaction self-managing their pain. Most patients reported independently self-managing their cancer pain; however, satisfaction with pain management was low for a large proportion of patients. Time since cancer diagnosis and ability to deal with frustration due to cancer pain were positively associated with cancer pain self-efficacy, whereas pain self-efficacy had a significant inverse correlation with cancer pain severity. Conclusions: Enhancing self-efficacy to self-manage under-treated cancer pain is important with implications for improving pain outcomes and quality of life. Further investigation on unmet needs and preferences for cancer pain self-management support is warranted.

Small cell lung cancer (SCLC) is a particular subtype of lung cancer with high mortality. Recent advances in understanding SCLC genomics and breakthroughs of immunotherapy have substantially expanded existing knowledge and treatment modalities. However, challenges associated with SCLC remain enigmatic and elusive. Most of the conventional drug discovery approaches targeting altered signaling pathways in SCLC end up in the ‘grave-yard of drug discovery’, which mandates exploring novel approaches beyond inhibiting cell signaling pathways. Epigenetic modifications have long been documented as the key contributors to the tumorigenesis of almost all types of cancer, including SCLC. The last decade witnessed an exponential increase in our understanding of epigenetic modifications for SCLC. The present review highlights the central role of epigenetic regulations in acquiring neoplastic phenotype, metastasis, aggressiveness, resistance to chemotherapy, and immunotherapeutic approaches of SCLC. Different types of epigenetic modifications (DNA/histone methylation or acetylation) that can serve as predictive biomarkers for prognostication, treatment stratification, neuroendocrine lineage determination, and development of potential SCLC therapies are also discussed. We also review the utility of epigenetic targets/epidrugs in combination with first-line chemotherapy and immunotherapy that are currently under investigation in preclinical and clinical studies. Altogether, the information presents the inclusive landscape of SCLC epigenetics and epidrugs that will help translate the knowledge of epigenetics to improve SCLC outcomes.

Objectives Cancer is the second leading cause of mortality in the world, and represents an economic, social and psychological burden. Scientific studies have focused on psychosocial coping mechanisms of patients and on factors improving their quality of life. Thus, the aim of the present study is to analyze the influence that spirituality would have on the quality of life of Lebanese cancer patients and to identify whether the influence on quality of life is mediated through a decreased depression. Methods This is a cross-sectional study targeting cancer patients in the hemato-oncology department of the Hotel-Dieu de France Hospital (Beirut, Lebanon). It is based on a questionnaire composed of three parts: EQ-5D-5L, PHQ-9, and FACIT-Sp-12. Likewise, a control group suffering from chronic diseases and treated in the hospital was questioned. Univariate and multivariate analysis were conducted to assess the relationship between the different questionnaires for controls and for cancer patients. Results Thirty-nine cancer patients and eight control patients were questioned. In the univariate analysis, there was no relationship between depression and spirituality nor for spirituality and quality of life. After controlling for depression, an inverse correlation between quality of life and spirituality was shown. Conclusions Our study is a pilot study which for the first time investigates the implication of depression in a “spirituality-quality of life” association. There is no clear association of spirituality with quality of life. In fact, the physical and psychological burden of chronically ill patients could exceed and render insignificant a possible impact of spirituality on quality of life.

Background: PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of a variety of solid tumors. Some clinical trials have also confirmed the excellent efficacy of PD- 1/PD-L1 inhibitors on lymphoma. However, the efficacy of PD-1/PD-L1 inhibitors on leukemia remains unclear. Main body: To understand the connection between PD-1/PD-L1 and leukemia better, this review concentrates on the up-regulated expression of PD-1/PD-L1 and the PD-1/PD-L1 blockade trials in participants with leukemia. PD-1/PD-L1 signal performs momentously negative immunoregulation of cancer, which can inhibit the activation of cytotoxic T cells and involve in the immune escape in tumors. Activated PD-1/PD-L1 may transduce negative intracellular signals to block the mitotic cycle and the development of T-cells. Several pathways are involved in these critical biochemical processes, including MAPK, calcium, PI3K/AKT, and so on. Lately, PD-1/PD-L1 antibodies have illustrated unprecedented curative effects on Hodgkin's lymphoma and some solid tumors. Specimens from patients with leukemia demonstrated the elevated level of PD-1/PD-L1 in T lymphocytes. This finding inspired hematologists to use PD-1/PD-L1 inhibitors for subjects suffering from leukemia. Some clinical trials have implied that PD-1/PD-L1 inhibitors could help patients fight against leukemia, however, other researchers have reported the opposite results. Conclusions: PD-1/PD-L1 is upregulated in leukemia, but the results regarding PD-1/PD-L1 blockade are mixed and more clinical trials are needed to be conducted.

Sexual dysfunction (SD) is widely reported by cancer survivors. However, this is an issue underestimated by doctors and the contribution of anticancer therapies for the development of SD in cancer survivors is understudied and poorly understood. Sexual function involves the activation of a neurovascular system that leads to penile erection in males and clitoral engorgement in females. Anticancer therapies can cause damage to the neurovascular circuit responsible for normal sexual function and thus, individual or combined therapies could play a role in the development of SD in all types of cancer survivors and not only those affected by genital cancers. In this review, the pathophysiology of SD and possible mechanisms underlying SD induced by anticancer therapies will be discussed. The effects of chemotherapy, radiotherapy and surgical interventions on the vasculature and nerves as well as their effects on sex hormones and inflammatory processes could link the biological effects of these interventions with SD. In conclusion, this review reports evidence that, despite psychological aspects and the disease itself, anticancer therapies are able to induce direct and indirect effects in males and females that could lead to SD in cancer survivors even after the end of the treatment.

The world-wide rate of incidence of cancer disease has been only modestly contested by the past and current preventive and interventional strategies. Hence, the global effort towards novel ideas to contain the disease still continues. Constituents of human diets have in recent years emerged as key regulators of carcinogenesis, with studies reporting their inhibitory potential against all the three stages vis-a-vis initiation, promotion and progression. Unlike drugs which usually act on single targets, these dietary factors have an advantage of multi-targeted effects and pleiotropic action mechanisms, which are effective against cancer that manifest as a micro-evolutionary and multi-factorial disease. Since most of the cellular targets have been identified and their consumption considered relatively safe, these diet-derived agents often appear as molecules of interest in repurposing strategies. Currently, many of these molecules are being investigated for their ability to influence the aberrant alterations in cell's epigenome for epigenetic therapy against cancer. Targeting the epigenetic regulators is a new paradigm in cancer chemoprevention which acts to reverse the warped-up epigenetic alterations in a cancer cell, thereby directing it towards a normal phenotype. In this review, we discuss the significance of dietary factors and natural products as chemopreventive agents. Further, we corroborate the experimental evidence from existing literature, reflecting the ability of a series of such molecules to act as epigenetic modifiers in cancer cells, by interfering with molecular events that map the epigenetic imprints such as DNA methylation, histone acetylation and non-coding RNA mediated gene regulation.

Background: The ubiquitin-proteasome system (UPS) is critical in cellular protein degradation and widely involved in the regulations of cancer hallmarks. Targeting the UPS pathway has emerged as a promising novel treatment in hematological malignancies and solid tumors. Objective: This review mainly focuses on the preclinical results of proteasome inhibitors in solid tumors. Methods: We analyzed the published articles associated with the anticancer results of proteasome inhibitors alone or combination chemotherapy in solid tumors. Important data presented in abstract form were also discussed in this review. Results/Conclusion: Proteasome inhibitors, such as bortezomib and carfilzomib, are highly effective in treating solid tumors. The anticancer efficacy is not limited to affect the proteasomal inhibition- associated signaling pathways but also widely involves the signaling pathways related to cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT). In addition, proteasome inhibitors overcome the conventional chemo-resistance of standard chemotherapeutics by inhibiting signaling pathways, such as NF-κB or PI3K/Akt. Combination chemotherapy of proteasome inhibitors and standard chemotherapeutics are widely investigated in multiple relapsed or chemo-resistant solid tumor types, such as breast cancer and pancreatic cancer. The proteasome inhibitors re-sensitize the standard chemotherapeutic regimens and induce synergistic anticancer effects. The development of novel proteasome inhibitors and delivery systems also improves the proteasome inhibitors’ anticancer efficacy in solid tumors. This review summarizes the current preclinical results of proteasome inhibitors in solid tumors and reveals the potential anticancer mechanisms.