Cancers In Different Organs Research Articles

Effects of simulated smoke condensate generated from combustion of selected military burn pit contents on human airway epithelial cells.

Exposure to military burn pit smoke during deployment is associated with different respiratory and non-respiratory diseases. However, information linking smoke exposure to human pulmonary health is lacking. This study examined the effects of simulated burn pit smoke condensates on human airway epithelial cells (HAECs) from twelve donors (smokers/non-smokers, biological female/male) cultured at an air-liquid interface and exposed to condensates from three simulated burn pit waste materials (cardboard, plywood, and plastic) incinerated at two combustion conditions: smoldering and flaming. Cellular gene expression was analyzed using bulk RNA sequencing, and basolateral media cytokine levels were assessed using multiplex immunoassay. Flaming smoke condensates caused more significant differentially expressed genes (DEGs) with plywood flaming smoke being the most potent in altering gene expression and modulating cytokine release. Cardboard and plywood flaming condensates primarily activated detoxification pathways, whereas plastic flaming affected genes related to anti-microbial and inflammatory responses. Correlation analysis between smoke condensate chemicals and gene expression to understand the underlying mechanism revealed crucial role of oxygenated polycyclic aromatic hydrocarbons (PAHs) and aluminum, molybdenum, and silicon elements; IL6 expression was positively correlated with most PAHs. Stratification of data based on HAEC donor demographics suggests that these affect gene expression changes. Enrichment analysis indicated similarity with several deployment-related presumptive and reported diseases, including asthma, emphysema, and cancer of different organs. This study highlights that simulated burn pit smoke exposure of HAECs causes gene expression changes indicative of deployment-related diseases with more pronounced effects seen in smokers and females. Future studies are needed to further characterize how sex and smoking status affect deployment-related diseases.

High performance calculation of nonlinear wave propagation on GPU for focused ultrasound treatment planning

High intensity focused ultrasound (HIFU) is very promising new technology that has many therapeutic application, and among them are the treatment of cancer in different organs without major side effects. Some of the limitations of HIFU are the long treatment time and incomplete ablation. High performance computing can help in this regard. Simulation of nonlinear wave propagation in three dimensional geometry is very time consuming process especially when shocks are presented. In the current work, we are going to present three dimensional parallel solver on GPU. Some examples for the simulation in a patient specific geometry will be also presented. The presented results can be used for the optimization of the treatment. For the validation of the results, ex-vivo and in-vivo experiments have been performed. It has been shown that large volume can be ablated within a short period of time.

The Role of Mitochondrial Dysfunction in Idiopathic Pulmonary Fibrosis: New Perspectives for a Challenging Disease.

Mitochondrial biology has always been a relevant field in chronic diseases such as fibrosis or cancer in different organs of the human body, not to mention the strong association between mitochondrial dysfunction and aging. With the development of new technologies and the emergence of new methodologies in the last few years, the role of mitochondria in pulmonary chronic diseases such as idiopathic pulmonary fibrosis (IPF) has taken an important position in the field. With this review, we will highlight the latest advances in mitochondrial research on pulmonary fibrosis, focusing on the role of the mitochondria in the aging lung, new proposals for mechanisms that support mitochondrial dysfunction as an important cause for IPF, mitochondrial dysfunction in different cell populations of the lung, and new proposals for treatment of the disease.

Possible cancer-causing capacity of COVID-19: Is SARS-CoV-2 an oncogenic agent?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown diverse life-threatening effects, most of which are considered short-term. In addition to its short-term effects, which has claimed many millions of lives since 2019, the long-term complications of this virus are still under investigation. Similar to many oncogenic viruses, it has been hypothesized that SARS-CoV-2 employs various strategies to cause cancer in different organs. These include leveraging the renin angiotensin system, altering tumor suppressing pathways by means of its nonstructural proteins, and triggering inflammatory cascades by enhancing cytokine production in the form of a “cytokine storm” paving the way for the emergence of cancer stem cells in target organs. Since infection with SARS-CoV-2 occurs in several organs either directly or indirectly, it is expected that cancer stem cells may develop in multiple organs. Thus, we have reviewed the impact of coronavirus disease 2019 (COVID-19) on the vulnerability and susceptibility of specific organs to cancer development. It is important to note that the cancer-related effects of SARS-CoV-2 proposed in this article are based on the ability of the virus and its proteins to cause cancer but that the long-term consequences of this infection will only be illustrated in the long run.

Development and Validation of CT-Based Radiomics Signature for Overall Survival Prediction in Multi-organ Cancer.

The malignant tumors in nature share some common morphological characteristics. Radiomics is not only images but also data; we think that a probability exists in a set of radiomics signatures extracted from CT scan images of one cancer tumor in one specific organ also be utilized for overall survival prediction in different types of cancers in different organs. The retrospective study enrolled four data sets of cancer patients in three different organs (420, 157, 137, and 191 patients for lung 1 training, lung 2 testing, and two external validation set: kidney and head and neck, respectively). In the training set, radiomics features were obtained from CT scan images, and essential features were chosen by LASSO algorithm. Univariable and multivariable analyses were then conducted to find a radiomics signature via Cox proportional hazard regression. The Kaplan-Meier curve was performed based on the risk score. The integrated time-dependent area under the ROC curve (iAUC) was calculated for each predictive model. In the training set, Kaplan-Meier curve classified patients as high or low-risk groups (p-value < 0.001; log-rank test). The risk score of radiomics signature was locked and independently evaluated in the testing set, and two external validation sets showed significant differences (p-value < 0.05; log-rank test). A combined model (radiomics + clinical) showed improved iAUC in lung 1, lung 2, head and neck, and kidney data set are 0.621 (95% CI 0.588, 0.654), 0.736 (95% CI 0.654, 0.819), 0.732 (95% CI 0.655, 0.809), and 0.834 (95% CI 0.722, 0.946), respectively. We believe that CT-based radiomics signatures for predicting overall survival in various cancer sites may exist.

Across-cancer specific immune responses induced by nanovaccines or microvaccines to prevent different cancers and cancer metastasis.

Metastatic cancers and recurrent cancers are diverse, different from primary cancers, and organ-dependent. However, how strong are across-cancer immune responses among different types of cancers remain unclear. Herein, vaccines-encapsulated-whole-components-of-tumor-tissue (VEWCOTT) were applied to demonstrate the across-cancer immune responses, thanks to inducing pan-clones T-cell immune responses. Either lung-cancer-tissue- or melanoma-tissue-based VEWCOTT simultaneously prevented melanoma, lung cancer, hepatoma, and metastatic cancer, which showed that strong across-cancer immune responses were induced. Both nanovaccines and microvaccines showed potent across-cancer prevention efficacy. VEWCOTT induced tumor-specific Tcells in peripheral immune organs and major organs, and adjusted the immune-microenvironment of cancer-colonized organs. In addition, the allograft of Tcells from VEWCOTT immunized mice to allogeneic naive mice efficiently prevent various cancers. Many neoantigens are shared by melanoma cells and lung cancer cells. Across-cancer immune responses exist among different types of cancers, and thus VEWCOTT has the advantage of simultaneously preventing cancer metastasis and cancers in different organs.

The Kv10.1 voltage-gated ion channel modeling based on control system theory

Abstract In this paper, we present a control system theory based modeling approach for the voltage-gated ion-channel Kv10.1 at different temperatures. Kv10.1 is expressed in the central nervous system and the brain of healthy humans. The study of the activity of this ion channel is important, because its activity is associated with the occurrence of cancer in different organs or tissues. According to systems and control theory, the voltage-gated channel Kv10.1 was assumed to be a linear time-invariant system and, as such, exhibits dynamic behavior. The experimental results show that Kv10.1 operates as a first-order model based on the input voltage step protocol and the measured macroscopic ion current output.

Study on the radiation detriment

Cancer incidence risks, lifetime effects and radiation detriments are determined for the whole population and various subpopulations as a result of acute and chronic exposure to low-LET radiation, taking into account the risk models, procedures and representative populations provided by ICRP. The results are given for solid cancers in different organs, as well as for soft tissue cancer in bone marrow. For most cancer sites a good agreement is obtained between the results of this study and the values published by the ICRP. The agreement with ICRP values is better for the whole population than for the working age population, where the results are systematically elevated. For chronic exposure, the years of life lost per radiation-induced cancer incidence are generally higher. In particular, this results in a radiation detriment for the whole population that is 30% higher than for acute exposure. The study reveals that risk quantities show a pronounced age dependence. The highest radiation risks are attributed to young persons; the lowest to persons in advanced ages. The total detriment imposed on people in different ages varies by a factor of about 30. The average values provided by the ICRP mask these variations and considerably underestimate radiation risks in childhood and adolescence. This also concerns the determination of the effective dose for persons in these age groups. Unlike the ICRP, which provides different nominal detriments for the whole population and the working age population, the results of this study do not support the use of different detriments for these populations.

Secondary Solid Cancers after Allogeneic Hematopoietic Stem Cell Transplantation: A Single Center Experience of 1374 Patients Including 812 Cord Blood Transplant Recipients

Background: Secondary solid cancer is one of the most important late complications among long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). Although age at HSCT, total body irradiation (TBI) as part of the conditioning regimens and chronic graft-versus-host diseases (GVHD) have been already reported as risk factors for secondary solid cancers, the impact of stem cell source has not been fully evaluated.Patients and Methods: We reviewed the medical records of Japanese adult patients who underwent allogeneic HSCT for the first time at the Toranomon Hospital between 1993 and 2015. Cumulative incidences of secondary solid cancers or GVHD were estimated, with death without developing secondary cancers or GVHD treated as a competing risk. The date of the first cancer in patients developing multiple metachronous secondary cancers was used in calculations of cumulative incidence. A step-wise multivariate approach was used to identify risk factors for secondary cancers. The variables considered were age at HSCT, sex, primary diseases, donor-type, conditioning regimens, TBI as part of the conditioning, grade II-IV acute GVHD and extensive chronic GVHD. Acute GVHD and chronic GVHD were considered as time-dependent covariates.Results: A total of 1374 patients were included in the analysis, with the median age of 54 years (16-82). Approximately two-thirds (64%) of the patients were male and were diagnosed with Acute leukemia/Myelodysplastic syndrome, respectively. Eight-hundred twelve (59.1%) patients underwent unrelated cord blood transplantation (UCBT), 313 (22.8%) underwent unrelated bone marrow transplantation (UBMT) and the remaining 249 (18.1%) underwent transplantation from a related donor. Half of the patients received reduced-intensity conditioning, and about 60% had any dose of total body irradiation. Cumulative incidence of grade II-IV acute GVHD at day 100 and extensive chronic GVHD at 2 years were 47.7% and 22.4%, respectively.Thirty-two patients developed secondary cancers at a median of 4.1 years (1.1months-14.8 years), four of who had two (2) or three (2) cancers in different organs. Overall, 38 cancers were identified. The most common sites of cancers were esophagus (9) and stomach (9), followed by oral (6), colon (3), skin (2), lung (2) and bladder (2). Cumulative incidence of secondary cancers at 5, 10, and 15 years after transplantation were 2.4%, 4.6%, and 10.8%, respectively. Compared with UBMT recipients, the risk of secondary cancers tended to be lower in transplant recipients from a related donor (HR 0.41, P=0.075) and was significantly lower in UCBT recipients (HR 0.45, P=0.035, Figure). Multivariate analysis revealed age ≥ 40 years (HR 9.3, P=0.027) and extensive chronic GVHD (HR 4.9, P<0.001) were identified as significant risk factors for secondary cancers.We also compared the incidence and risk factors for secondary cancers between UCBT (671) and UBMT (217) recipients who aged ≥ 40 years and underwent transplantation after 2002, because UCBT was introduced in 2002 at our hospital and only one case of secondary cancer was identified in transplant recipients from a related donor thereafter. The median age of UCBT recipients was higher than that of UBMT recipients (60 years vs. 56 years, P<0.001). Cumulative incidence of secondary cancers was 9.6%, which was significantly lower after UCBT compared to UBMT (5.2% vs. 18.4%, P=0.014). Extensive chronic GVHD was identified as a significant risk factor for secondary cancers (HR 3.38, P=0.04). Cumulative incidence of extensive chronic GVHD at 2 years was significantly lower after UCBT than after UBMT (12.3% vs. 39.1%, P<0.001), and extensive chronic GVHD had no significant impact on the risk of secondary cancers after UCBT (HR 2.8, P=0.134), in contrast with a strong association between extensive chronic GVHD and the development of secondary cancers after UBMT (HR 5.6, P=0.025).Conclusions: Endscopic screening is important as part of lifelong follow-up, especially for patients who are aged 40 and older or have extensive chronic GVHD. Despite the limitation of relatively shorter follow-up, the use of cord blood may have potential for reducing the risk of secondary solid cancers, probably because of lower frequency of extensive chronic GVHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

WWC Proteins: Important Regulators of Hippo Signaling in Cancer.

Simple SummaryThe conserved Hippo pathway regulates cell proliferation and apoptosis via a complex interplay of transcriptional activities, post-translational protein modifications, specific protein–protein interactions and cellular transport processes. Deregulating this highly balanced system can lead to hyperproliferation, organ overgrowth and cancer. Although WWC proteins are known as components of the Hippo signaling pathway, their association with tumorigenesis is often neglected. This review aims to summarize the current knowledge on WWC proteins and their contribution to Hippo signaling in the context of cancer.The Hippo signaling pathway is known to regulate cell differentiation, proliferation and apoptosis. Whereas activation of the Hippo signaling pathway leads to phosphorylation and cytoplasmic retention of the transcriptional coactivator YAP, decreased Hippo signaling results in nuclear import of YAP and subsequent transcription of pro-proliferative genes. Hence, a dynamic and precise regulation of the Hippo signaling pathway is crucial for organ size control and the prevention of tumor formation. The transcriptional activity of YAP is controlled by a growing number of upstream regulators including the family of WWC proteins. WWC1, WWC2 and WWC3 represent cytosolic scaffolding proteins involved in intracellular transport processes and different signal transduction pathways. Earlier in vitro experiments demonstrated that WWC proteins positively regulate the Hippo pathway via the activation of large tumor suppressor kinases 1/2 (LATS1/2) kinases and the subsequent cytoplasmic accumulation of phosphorylated YAP. Later, reduced WWC expression and subsequent high YAP activity were shown to correlate with the progression of human cancer in different organs. Although the function of WWC proteins as upstream regulators of Hippo signaling was confirmed in various studies, their important role as tumor modulators is often overlooked. This review has been designed to provide an update on the published data linking WWC1, WWC2 and WWC3 to cancer, with a focus on Hippo pathway-dependent mechanisms.

Testicular morphometry of rats with Walker 256 tumor supplemented with L-glutamine.

Glutamine is often used to treat metabolic changes associated with anorexia-cachexia syndrome in patients with malignant neoplasms. Walker 256 tumor is an excellent model for studying these changes associated with cancer in different organs, including injuries in testicular functions. However, the effects of supplementing glutamine on testicular morphometry in this model have not yet been investigated. Thus, the objective of this study was to evaluate the effect of L-glutamine supplementation on testicular morphometry in rats transplanted with Walker 256 tumor cells. Forty puberty Wistar rats were divided into four groups: control without L-glutamine (C); control supplemented with L-glutamine (CG); inoculated with Walker 256 tumor cells (WT) and inoculated with Walker 256 tumor cells and supplemented with L-glutamine (WTG). The testicles were removed, weighed, fixed in Bouin, and included in paraffin for histomorphometric analysis. Walker 256 tumor caused quantitative changes in the tubular and intertubular compartments and tunica albuginea, with reductions in the percentages of lumen and tunica albuginea, number of Sertoli cells per gram of testis; number of Leydig cells; percentage of blood vessels and connective tissue in intertubule. However, glutamine supplementation prevented part of these changes caused by the tumor, presenting mainly a protective effect on the tunica albuginea and percentage of blood and lymph vessels in the intertubule. These results indicate the potential of L-glutamine was able to recover for testicular dysfunction associated with cancer.

A Combined Effect of Expression Levels of Obesity-Related Genes and Clinical Factors on Cancer Survival Rate.

Obesity is directly associated with the risk of cancer in different organs, including breast, colon, and kidney. However, adipocytes could be utilized to control progression for some types of cancer, such as leukemia and breast cancer. To explore the potential correlation between adipocytes and cancer, the combined effect of expression levels of obesity-related genes and clinical factors (i.e., gender, race, menopausal status, history of smoking, tumor grade, body mass index (BMI), and history of drinking) on cancer survival rate was systemically studied. The expression levels of obesity-related genes in cancer tissues and normal tissues were downloaded from The Cancer Genome Atlas (TCGA). Kaplan–Meier curves were plotted using R programming language. The log-rank test was applied to explore the correlation between different clinical subgroups. The overexpression of the nine obesity-related genes (MC4R, TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, FTO, PCSK1, and GPR120) may associate with tumor-promoting factors in some organs (head and neck, gastrointestinal tract, liver, and gallbladder). Underexpressed LEPR, NEGR1, TMEM18, and SH2B1 genes prevented the progression and metastasis of kidney cancer. The combined effect of clinical factors and the expression levels of obesity-related genes on patients' survival was found to be significant. Our outcomes suggested that the alternations of DNA methylation patterns could result in the changes of expression levels of obesity-related genes, playing a critical role in tumor progression. The results of the current study may be utilized to supplement precision and personalized medicine, as well as provide novel insights for the development of treatment approaches for cancer.

Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study

SummaryBackgroundEvidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence.MethodsThis study was done in a population-based cohort of 50 045 individuals aged 40–75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types.FindingsDuring a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24–1·58), gastrointestinal cancers (1·31, 1·11–1·55), and respiratory cancers (2·28, 1·58–3·30) in a dose-dependent manner (ptrend<0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06–1·80), gastric (1·36, 1·03–1·79), lung (2·21, 1·44–3·39), bladder (2·86, 1·47–5·55), and laryngeal (2·53, 1·21–5·29) cancers in a dose-dependent manner (ptrend<0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23–5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00–4·63) and liver (2·46, 1·23–4·95) cancers in a dose-dependent manner (prend<0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status.InterpretationOpium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types.FundingWorld Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer.

The therapeutic effects of blocking IGF-R1 on mice model of skin cancer

Background and objectives The incidence of skin cancer has raised in the last few years. One of the important growth factors found in the skin layers is insulin-like growth factor (IGF)-1. It is directly linked with many cancers in different organs. Therefore, we aimed to explore the therapeutic effects of blocking IGF-1 receptor (IGF-R1) pathway by PQ401 in skin cancer as well as studying its effect on tumor invasion markers. Materials and methods We experimentally induced skin cancer in mice by the application of 7,12-dimethylbenz (a) anthracene. Skin samples were removed for determination of gen and protein expression of IGF-1, IGF-R1, glypican-3, MMP9, syndecan-1 and fascin-1 by Western blot and PCR. Moreover, skin sections were stained with hematoxylin/eosin and Mallory. Results Treatment with PQ401 blocked the expression of IGF-R1 in the skin, which is associated with reduction in the skin cancer-induced tumors and scratches. In addition, PQ401 ameliorated skin cancer induced formation of epidermal atypia and hyperplasia. PQ401 reduced both gene and protein expression of the tumor invasion markers, MMP9, syndecan-1 and fascin-1, without affecting gene and protein expression of glypican-3 and IGF-1 in skin cancer group. Conclusion Blocking IGF-R1 has therapeutic effects against experimental skin cancer induced in mice. In addition, blocking IGF = R1 attenuated skin cancer-induced activation of tumor invasion markers. Key points IGF-1/IGF-R1is highly expressed in different cancers as skin cancer. Blocking IGF-R1 production ameliorated skin cancer. Blocking IGF-R1 attenuated skin cancer-induced activation of tumor invasion markers.

Bladder tissue characterization using probe-based Raman spectroscopy: Evaluation of tissue heterogeneity and influence on the model prediction.

Existing approaches for early‐stage bladder tumor diagnosis largely depend on invasive and time‐consuming procedures, resulting in hospitalization, bleeding, bladder perforation, infection and other health risks for the patient. The reduction of current risk factors, while maintaining or even improving the diagnostic precision, is an underlying factor in clinical instrumentation research. For example, for clinic surveillance of patients with a history of noninvasive bladder tumors real‐time tumor diagnosis can enable immediate laser‐based removal of tumors using flexible cystoscopes in the outpatient clinic. Therefore, novel diagnostic modalities are required that can provide real‐time in vivo tumor diagnosis. Raman spectroscopy provides biochemical information of tissue samples ex vivo and in vivo and without the need for complicated sample preparation and staining procedures. For the past decade there has been a rise in applications to diagnose and characterize early cancer in different organs, such as in head and neck, colon and stomach, but also different pathologies, for example, inflammation and atherosclerotic plaques. Bladder pathology has also been studied but only with little attention to aspects that can influence the diagnosis, such as tissue heterogeneity, data preprocessing and model development. The present study presents a clinical investigative study on bladder biopsies to characterize the tumor grading ex vivo, using a compact fiber probe‐based imaging Raman system, as a crucial step towards in vivo Raman endoscopy. Furthermore, this study presents an evaluation of the tissue heterogeneity of highly fluorescent bladder tissues, and the multivariate statistical analysis for discrimination between nontumor tissue, and low‐ and high‐grade tumor.

Targeting Long Non-Coding RNAs in Nervous System Cancers: New Insights in Prognosis, Diagnosis and Therapy.

Long non-coding RNAs (lncRNAs) constitute one of the most broad and diverse classes of cellular transcripts, playing key roles as regulatory molecules in many biological processes. Although the biology of lncRNAs is a new and emerging field of research, several studies have already shown that alterations in the expression of lncRNAs are associated with the development and progression of cancer in different organs and tissues, including central and peripheral nervous system. In this review, we summarize the oncogenic and tumor suppressive roles of lncRNAs in malignant tumors of the nervous system, such as glioma and neuroblastoma, focusing on their functional interactions with DNA, other RNA and protein molecules. We further discuss the potential use of lncRNAs as biomarkers for diagnosis, prognosis and tumor treatment. Gaining insight into the functional association between nervous system malignancies and lncRNAs could offer new perspectives to the development of promising therapeutic tools against cancer.

Analysis of mortality from cancer in the regional context of Slovakia

One of the dominant death causes, which contributes significantly to the mortality of the Slovak population, is cancer mortality. In the presence of cancers, we can find geographical differences i.e. the cancer of different organs has a different frequency of occurrence in different parts of Slovakia. It may be agreed that the fight against cancers, if it is to be complex, must include a spatial aspect and this is best applied in the field of medical geography. The solution of the development of cancer mortality in Slovakia can be considered a relevant topic of geographic research. Data on cancer mortality at the district level were used from the database of the Statistical Office of the Slovak Republic. The aim of the article is to assess the spatial aspect of cancers in the districts of Slovakia applying the standardized mortality rate. The standardized mortality rate will be analysed in terms of gender structure of population. The time horizon for standardized mortality rate comparison was set for the periods of 2001-2008, 2009-2017 and 2001-2017. From the perspective of the research of this topic it is important to apply specific analytical methods which include, for example, spatial autocorrelation.

Breast cancer and synchronous multiple primary lung adenocarcinomas with heterogeneous mutations: a case report

BackgroundMultiple primary malignant tumors (MPMT) refers to the presence of two or more primary cancers of different organs in the same patient. MPMT is a sparse disease in the past, but there has been a gradual increase in the morbidity. Since multiple primary malignant tumors treatment methods differ, it is essential for clinicians to be able to distinguish between separate primary lesions and metastasis.Case presentationWe present the case of a 57-year-old woman with MPMT presenting with cancer in the left breast and synchronous double primary lung adenocarcinomas. We used IHC and epidermal growth factor receptor(EGFR)mutation to analyze genomic alteration profiles in the patient to validate the difference among the pathological assessments and the clinical differences between double primary lesions of lung and breast. EGFR gene analysis of breast cancer lesion revealed no mutations. The left and right lower lobe lung adenocarcinomas contained EGFR gene mutations: an L858R point mutation in exon 21 in the left lesion and a deletion mutation in exon 19 in the right lesion. The breast cancer and both lung adenocarcinomas were surgically resected. To date, the patient has remained disease-free.ConclusionsBoth pathological and molecular assessment adapted in the current study appeared necessary. Mutational analysis of the EGFR gene provided important information not only in the diagnosis and but also in the treatment of MPMT.

Alcohol-associated cancer and deregulation of Pol III genes

Emerging evidence indicates that alcohol intake is associated with human cancers in different organs. However, the molecular mechanism of alcohol-associated human cancers remains to be elucidated. Here, this paper aimed to clarify a novel mechanism of alcohol-promoted cell transformation and tumor development. Alcohol induces JNK1 activation and increases cellular levels of c-Jun to upregulate Brf1 expression and Pol III gene transcription, leading to an enhancement of rates of cell transformation and tumor formation.

Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway.

Long-term exposure to arsenic has been linked to cancer in different organs and tissues, including skin. Here, non-malignant human keratinocytes (HaCaT) were exposed to arsenic and its effects on microRNAs (miRNAs; miR) expression were analyzed via miRCURY LNA array analyses. A total of 30 miRNAs were found differentially expressed in arsenic-treated cells, as compared to untreated controls. Among the up-regulated miRNAs, miR-21, miR-200a and miR-141, are well known to be involved in carcinogenesis. Additional findings confirmed that those three miRNAs were indeed up-regulated in arsenic-stimulated keratinocytes as demonstrated by quantitative PCR assay. Furthermore, bioinformatics analysis of both potential cancer-related pathways and targeted genes affected by miR-21, miR-200a and/or miR-141 was performed. Results revealed that miR-21, miR-200a and miR-141 are implicated in skin carcinogenesis related with melanoma development. Conclusively, our results indicate that arsenic-treated keratinocytes exhibited alteration in the miRNAs expression profile and that miR-21, miR-200a and miR-141 could be promising early biomarkers of the epithelial phenotype of cancer cells and they could be potential novel targets for melanoma therapeutic interventions.