Development Of Cancer In Patients Research Articles

Circulating microRNAs for early detection of hepatitis B-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major challenge for global health. Indeed, HCC represents the third leading and fastest rising cause of cancer death worldwide (1). About 90% of HCC cases can be associated with a well-characterized underlying risk factor including chronic hepatitis B, hepatitis C, ethanol consumption, aflatoxin exposure, non-alcoholic fatty liver disease, metabolic diseases like diabetes, and hereditary liver disease (1-3). Although the risk of developing HCC can be reduced in patients by treatment of the underlying cause, e.g., by viral clearance, strategies to prevent cancer development in patients with advanced fibrosis and established cirrhosis are still lacking (4). Furthermore, despite the recent improvements, treatment options for HCC remain largely unsatisfactory (5). Early diagnosis through surveillance of at-risk patients increases the chance of effective therapy. Clinical practice guidelines recommend periodic ultrasound-based surveillance of patients with cirrhosis (6). However, ultrasound detection of small liver tumors can be challenging and depends on the expertise of the operator. Therefore, several non-invasive biomarkers have been assessed for their utility in determining HCC risk and/or detecting HCC at early stages. Alpha-fetoprotein (AFP) is the most widely used diagnostic serum marker for HCC. However, since its diagnostic and predictive value is largely limited by the presence of AFP-negative HCC as well as the impact of the underlying liver disease (2,6), its use for HCC surveillance is currently not recommended by American and European guidelines. Thus there is an unmet need for novel serum biomarkers for HCC diagnosis capable of increasing the diagnostic and predictive power in surveillance programs.

Extrahepatic cancer risk among patients with liver cirrhosis in Taiwan: A nationwide population-based study.

1564 Background: Cirrhosis is a well-known risk factor of hepatocellular carcinoma. However, the risk of extra-hepatic cancers (EHCs) is not clear in cirrhotic patients. This study is aimed to identify the risk and sites of EHCs among cirrhotic patients. Methods: Newly diagnosed cirrhotic patients between 2000 and 2011 were recruited from Taiwan's nationwide health insurance database. Patients aged < 20 years and those with antecedent malignancies were excluded. To avoid surveillance bias, EHCs that developed within one year were also excluded in further analysis. Standardized incidence ratios (SIRs) of EHCs in these patients were calculated by comparing to the EHC incidence in the general population. Univariate and multivariate Cox proportional hazards models were applied to find the predictors of EHCs development among patients with cirrhosis. Results: During the 12-year study period, 859 EHCs developed among 13,729 cirrhotic patients, with a median follow-up period of 4.44 years. The SIR for all patients was 2.17 (95% confidence interval [CI] 2.03-2.32), for cirrhosis due to alcohol 3.43 (95% CI 3.02-3.89), for hepatitis B 1.81 (95% CI 1.51-2.15) and for hepatitis C 1.83 (95% CI 1.52-2.19). The SIRs for cancers of esophagus (4.60), head and neck (2.43), skin (1.99), stomach (1.95), bladder (1.66), breasts (1.46), and lung and mediastinum (1.42) were significantly increased. Multivariate analysis showed that age ≥ 50 years (adjusted hazard ratio [HR] 2.26, 95% CI 1.85-2.75), being male (HR 1.57, 95% CI 1.29-1.90), and chronic obstructive pulmonary disease (HR 1.29, 95% CI 1.06-1.56) were independent factors. Conclusions: This largest cohort study demonstrated an increasing risk of EHCs among cirrhotic patients, especially cirrhosis due to alcohol. Risk factors for cancer development in patients with cirrhosis. Variables Multivariate analysis HR (95% CI) P Value Age ≥ 50 2.26 (1.85-2.75) < 0.001 Sex (male) 1.57 (1.29-1.90) < 0.001 Comorbidities Diabetes mellitus 1.15 (0.94-1.40) 0.165 COPD 1.29 (1.06-1.56) 0.011 Autoimmune diseases 0.86 (0.61-1.21) 0.382 Dyslipidemia 1.00 (0.82-1.22) 0.998 Chronic kidney disease 0.95 (0.74-1.21) 0.658 COPD: chronic obstructive pulmonary disease

Scleroderma of geriatric age and scleroderma-like paraneoplastic syndrome - description of two cases.

Systemic sclerosis (Ssc) is an autoimmune connective tissue disease of unknown origin, characterized by progressive fibrosis of the skin and internal organs.Immune reactions taking part in Ssc pathogenesis may contribute to cancer development; therefore patients with risk factors for this disease require observation for a neoplastic process. On the other hand, symptoms of Ssc may be a mask of various cancers. Differentiating between the idiopathic form of Ssc and scleroderma-like paraneoplastic syndrome often causes a lot of difficulties.The article presents two cases of Ssc at the beginning of the disease after 60 years of age. The first case was diagnosed as Ssc, whereas in the second case the defined diagnosis was scleroderma-like syndrome in the course of colorectal cancer. This paper presents an analysis of differential diagnostic procedures which were performed and led to the final diagnosis, mentions types of cancers co-occurring with Ssc and suggests a screening scheme for cancer development in patients with a diagnosis of Ssc.

A Zebrafish Model of 5q-Syndrome Using CRISPR/Cas9 Targeting RPS14 Reveals a p53-Independent and p53-Dependent Mechanism of Erythroid Failure

5q-syndrome is a distinct form of myelodysplastic syndrome (MDS) where a deletion on chromosome 5 is the underlying cause. MDS is characterized by bone marrow failures, including macrocytic anemia. Genetic mapping and studies using various models support the notion that ribosomal protein S14 (RPS14) is the candidate gene for the erythroid failure. Targeted disruption of RPS14 causes an increase in p53 activity and p53-mediated apoptosis, similar to what is observed with other ribosomal proteins. However, due to the higher risk for cancer development in patients with ribosome deficiency, targeting the p53 pathway is not a viable treatment option. To better understand the pathology of RPS14 deficiency in 5q-deletion, we generated a zebrafish model harboring a mutation in the RPS14 gene. This model mirrors the anemic phenotype seen in 5q-syndrome. Moreover, the anemia is due to a late-stage erythropoietic defect, where the erythropoietic defect is initially p53-independent and then becomes p53-dependent. Finally, we demonstrate the versatility of this model to test various pharmacological agents, such as RAP-011, L-leucine, and dexamethasone in order to identify molecules that can reverse the anemic phenotype.

Report of the Japan diabetes society/Japanese cancer association joint committee on diabetes and cancer, Second report.

The Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer published its first report in July 2013 on the epidemiological assessment of the associations of diabetes with cancer risk/prognosis, the common risk factors for diabetes and cancer, and cancer risk associated with diabetes treatment. The Joint Committee continued its work to assess the role of glycemic control in the development of cancer in patients with diabetes. This review shows that high‐quality evidence examining the association between glycemic control and cancer risk is lacking.In 2014, the Japan Diabetes Society (JDS) and the Japanese Cancer Association (JCA) restarted the JDS/JCA Joint Committee on Diabetes and Cancer, which published the second committee report in Japanese [1]. This is the English version of that report. This article has been jointly published in Diabetology International (doi:10.1007/s13340‐016‐0257‐z) and Cancer Science by the Japan Diabetes Society and the Japanese Cancer Association.Members of the JDS/JCA Joint Committee on Diabetes and Cancer. JDS: Mitsuhiko Noda, Kohjiro Ueki, Masato Kasuga, Naoko Tajima, and Ken Ohashi; Editorial collaborators: Atsushi Goto and Hiroshi Noto; JCA: Ryuichi Sakai, Shoichiro Tsugane, Nobuyuki Hamajima, Kazuo Tajima, Kohzoh Imai, and Hitoshi Nakagama.

Report of the Japan Diabetes Society (JDS)/Japanese Cancer Association (JCA) Joint Committee on Diabetes and Cancer, Second Report.

The Japan Diabetes Society (JDS)/Japanese Cancer Association (JCA) Joint Committee on Diabetes and Cancer published its first report in July 2013 on the epidemiological assessment of the associations of diabetes with cancer risk/prognosis, the common risk factors for diabetes and cancer, and cancer risk associated with diabetes treatment The JDS/JCA Joint Committee continued its work to assess the role of glycemic control in the development of cancer in patients with diabetes. This review shows that high-quality evidence examining the association between glycemic control and cancer risk is lacking.

Cancer Risk in Patients With Empyema: A Nationwide Population-Based Study.

This study aimed to evaluate cancer risk and possible risk factors in patients diagnosed with empyema. A total of 31,636 patients with newly diagnosed empyema between January 1, 1999 and December 31, 2010 were included in this study. Standardized incidence ratios (SIRs) were calculated to compare the cancer incidence in these empyema patients to that in the general population. Adjusted hazard ratios were also calculated to investigate whether characteristics increased cancer risk. During the 12-year study period, 2,654 cancers occurred in 31,636 patients with empyema, yielding an SIR of 2.67 (95% confidence interval [CI] 2.57-2.78). We excluded cancer that occurred within 1 year to avoid surveillance bias. The cancer risk remained significantly increased (SIR 1.50, 95% CI 1.41-1.58). Specifically, patients with empyema had higher SIR of cancers of the head and neck (1.50, 95% CI 1.41-1.58), esophagus (2.56, 95% CI 1.92-3.33), stomach (1.49, 95% CI 1.16-1.89), liver and biliary tract (2.18, 95% CI 1.93-2.45), and lung and mediastinum (1.62, 95% CI 1.39-1.86). Age ≥ 60, male sex, diabetes mellitus, and liver cirrhosis were independent risk factors for cancer development. Our study demonstrates an increased incidence of cancer development in patients with empyema, and patients' age ≥ 60, men, and those with diabetes mellitus and liver cirrhosis showed a higher incidence of developing cancer compared to the general population. The association between such kind of infection and secondary malignancy may be elucidated by further study.

Erlotinib and the Risk of Oral Cancer: The Erlotinib Prevention of Oral Cancer (EPOC) Randomized Clinical Trial.

Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking. To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs. The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients. Oral erlotinib treatment (150 mg/d) or placebo for 12 months. Oral cancer-free survival (CFS). A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib-treated patients were 74% and 70%, respectively (hazard ratio [HR], 1.27; 95% CI, 0.68-2.38; P = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74% vs 87%, HR, 2.19; 95% CI, 1.25-3.83; P = .01). Increased EGFR gene copy number correlated with LOH-positive status (P < .001) and lower CFS (P = .01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P = .01). In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased EGFR copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-EGFR-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting. clinicaltrials.gov Identifier: NCT00402779.

Current understanding of mdig/MINA in human cancers.

Mineral dust-induced gene, mdig has recently been identified and is known to be overexpressed in a majority of human cancers and holds predictive power in the poor prognosis of the disease. Mdig is an environmentally expressed gene that is involved in cell proliferation, neoplastic transformation and immune regulation. With the advancement in deciphering the prognostic role of mdig in human cancers, our understanding on how mdig renders a normal cell to undergo malignant transformation is still very limited. This article reviews the current knowledge of the mdig gene in context to human neoplasias and its relation to the clinico-pathologic factors predicting the outcome of the disease in patients. It also emphasizes on the promising role of mdig that can serve as a potential candidate for biomarker discovery and as a therapeutic target in inflammation and cancers. Considering the recent advances in understanding the underlying mechanisms of tumor formation, more preclinical and clinical research is required to validate the potential of using mdig as a novel biological target of therapeutic and diagnostic value. Expression level of mdig influences the prognosis of several human cancers especially cancers of the breast and lung. Evaluation of mdig in cancers can offer novel biomarker with potential therapeutic interventions for the early assessment of cancer development in patients.

Abstract 1513: ALDH1 and podoplanin expression in oral leukoplakia: Correlate with malignant transformaion risk

Abstract Oral leukoplakia (OL) is the clinically diagnosed preneoplastic lesion in the oral cavity with an increased oral cancer risk. However, the risk of malignant transformation of OL is still difficult to assess. The objective of this study was to examine the expression patterns of ALDH1 and Podoplanin (PD) and determine their role in predicting oral cancer development in patients with OL. In a retrospective follow-up study, the expression patterns of ALDH1 and PD were determined using immunohistochemistry in samples from 79 patients with OL, including patients with untransformed lesions (n = 42) and patients with malignant transformed lesions (n = 37). The association between protein expression patterns and clinicopathologic parameters including oral cancer free survival (OCFS) was analyzed during a mean follow up period of 3.5 years. ALDH1 and PD expression was observed in 48 (61%) and 53 (67%) patients respectively. Kaplan-Meier analysis showed that the expression of ALDH1 and PD was correlated with the risk of progression to oral cancer (P = &amp;lt; 0.05). Multivariate analysis revealed that ALDH1 and PD expression was associated with 3.02 folds and 2.62 folds of increase risk of malignant transformation, respectively. Meanwhile, the malignant transformation risk of OL was considerably higher in cases with both ALDH1 and PD expression (P = 0.000). Taken together, our data indicated that ALDH1 and PD expression patterns in OL were associated with oral cancer development, suggesting that ALDH1 and PD could be useful biomarkers to identify OL patient with substantially high oral cancer risk. Citation Format: Umma Habiba, Masanobu Shindoh. ALDH1 and podoplanin expression in oral leukoplakia: Correlate with malignant transformaion risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1513. doi:10.1158/1538-7445.AM2015-1513

Su1210 The Prognostic Value of the Natural Killers (NK-Cells) in Case of Ulcerative Colitis Depending on Its Severity

The goal: to study the quantitative parameters of the effector NKand NKT-cells of ulcerative colitis patients in case of different activity rate of autoimmune process. Materials and methods: From 2011 till 2012 42 ulcerative colitis (UC) patients being under treatment in the Intestines Pathology Department in CSRIG (Central Scientific Research Institute of Gastroenterology) were studied. 32 of them men, 10 women. The age of the patients ranged from 19 to 70 years, average age 41,3±2,3 (M±σ). The diagnosis was verified using data of clinical, laboratory, immunological, histological and instrumental methods of research. Immunophenotyping of NKand NKT-cells by the method of flow cytometry using twoparameter reagents (CD3-FITC/CD16/56-PE and CD3+FITC/CD16/56-PE, «Bekman Coulter») was performed. The sample was analyzed by flow cytometers FACSCalibur («Bekman Dickinson»). The statistic data analysis was performed using the computer program «STATISTICA 6.0», the statistical significance of the values was verified by the Student t-test. Results: The analysis of lymphocyte parameters determining the killer effect without the help of antigen recognizing receptor of natural killers (NK-cells) showed a significant (p<0,001) reduction of relative and absolute quantity of lymphocytes expressing CD3-CD16+56+ to 6,0±1,2% in patients with heavy UC severity comparing to the patients with mild and medium severity (12,3±1,9 and 17,5±2,5% respectively). A statistically significant reduction (up to 4,6±1,4%, p<0,001) of relative quantity of the CD3+CD16+56+NKT-cells was observed during the study of the patients with heavy UC severity comparing to the patients with mild severity (9,4±1,4%); there was no significant difference between medium and heavy UC severity (p=0,834). Insufficient functioning of natural killers (NK-cells) should be taken into account in connection to the problem of colorectal cancer development in patients with long-lasting progressive state of UC. Conclusion: The obtained data show the decrease of relative and absolute abundance of NKand NKT-cells in patients with heavy UC severity, but it should be noted that apart from the quantitative parameters an important role in the

Over Expression of HuR and Podoplanin May Predict The Development of Oral Cancer in Patients with Oral Preneoplastic Lesion

Over Expression of HuR and Podoplanin May Predict The Development of Oral Cancer in Patients with Oral Preneoplastic Lesion

Gastric Neoplasia during Anti-TNF Therapy for Crohn’s Disease: Casual Event?

The increase risk of cancer development in patients with inflammatory intestinal disease (IBD) has already studied for decades. The anti-TNF therapy has changed the treatment strategy of IBD. By using on a larger scale and for a longer time, the anti-TNF raised concern over its potential adverse events. A male Crohn’s disease (CD) patient, 55 years old, diagnosed for nine years, treated with infliximab for 6 years. In 2011, he underwent a nupper endoscopy (UE) which showed flat erosive gastritis with moderate intensity in antrum, gastric polyps and gastric erosion. Pathological examination revealed a chronic gastritis in erosive activity and search for Helicobacter pylori resulted positive. In May 2014, the patient was asymptomatic, when it held UE, which showed suggestive lesion of early gastric cancer, measuring 1.5 cm and search for Helicobacter pylori negative. Histopathological exams confirmed the adenocarcinoma. The patient underwent to a laparoscopic surgery (total gastrectomy with lymphadenectomy and reconstruction Roux-en-Y). Risk factors for the development of gastric cancer in general population are already well defined. However studying a possible association among CD and the different therapeutic modalities used in the treatment of this disease with gastric cancer appearance is important to set specific assessment strategies, prevention and follow-up. While there is no consensus on a proper monitoring for gastric cancer prevention in these patients, individualized conduct, taking into account individual characteristics, family record and other risk factors, should be adopted to avoid unfavorable outcomes in CD patients.

Risk-reducing surgery in hereditary gynecological cancer: Clinical applications in Lynch syndrome and hereditary breast and ovarian cancer.

Risk-reducing surgery (RRS) is defined as a prophylactic approach with removal of organs at high risk of developing cancer, which is performed in cases without lesions or absence of clinically significant lesions. Hereditary gynecological cancers for which RRS is performed include hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. For HBOC, RRS in the United States (US) is recommended for women with mutations in the breast cancer susceptibility (BRCA)1 and BRCA2 genes and bilateral salpingo-oophorectomy (BSO) is generally performed. This procedure may reduce the risk of breast, ovarian, Fallopian tube and primary peritoneal cancer, although ovarian deficiency symptoms occur postoperatively. For Lynch syndrome, RRS in the US is considered for postmenopausal women or for women who do not desire to bear children and BSO and hysterectomy are usually performed. This approach may reduce the risk of endometrial and ovarian cancer, although ovarian deficiency symptoms also occur. For RRS, there are several issues that must be addressed to reduce the risk of cancer development in patients with HBOC or Lynch syndrome. To the best of our knowledge, this is the first review to discuss RRS with a focus on hereditary gynecological cancer.

The metastasis promoting protein S100A4 levels associate with disease activity rather than cancer development in patients with idiopathic inflammatory myopathies.

IntroductionThe aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis.MethodsSerum levels of S100A4 were determined in 43 dermatomyositis (DM), 39 polymyositis (PM) and 22 cancer associated myositis (CAM) patients as well as in 77 healthy controls. The associations between S100A4 levels, inflammation, disease activity, muscle strength and cancer development were evaluated.ResultsAll myositis patients had significantly higher serum levels of S100A4 protein compared to healthy controls (median (IQR): 31.5 (17.4 to 59.5) versus 23.8 (14.5 to 33.7) ng/ml, P <0.05). In patients with PM, serum levels of S100A4 protein were significantly higher than in healthy controls (41.6 (24.2 to 123.1) versus 23.8 (14.5 to 33.7) ng/ml; P <0.001) as well as in patients with DM (26.7 (11.3 to 47.5) ng/ml; P <0.05). The levels of S100A4 were comparable between myositis with and without cancer. In all myositis patients, serum S100A4 levels correlated with MYOsitis disease ACTivity assessment (MYOACT) score (r = 0.34; P = 0.001), constitutional (r = 0.30; P = 0.003), pulmonary (r = 0.43; P = 0.0001) and extramuscular disease activity (r = 0.36; P = 0.0001), as well as with creatine phosphokinase (r = 0.27; P = 0.015) and lactate dehydrogenase (r = 0.37; P = 0.002) or c-reactive protein (CRP) levels (r = 0.24; P = 0.038). Multiple regression analysis showed significant association between S100A4 serum levels and extramuscular disease activity (β = 0.552; P = 0.002) in PM patients and with MYOACT (β = 0.557; P = 0.003) and CRP levels (β = 0.391; P = 0.029) in DM patients.ConclusionsCirculating levels of S100A4 are elevated in patients with myositis and associate with several disease activity parameters, particularly with extramuscular components. No relation between S100A4 levels and presence of cancer associated myositis was found.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0468-2) contains supplementary material, which is available to authorized users.

PTU-141 Gastric Intestinal Metaplasia: A Retrospective Analysis In A District General Hospital In The United Kingdom

IntroductionGastric intestinal metaplasia (IM) is part of a carcinogenesis sequence leading to gastric cancer. Recent evidence-based European Society of Gastrointestinal Endoscopy (ESGE) guidelines highlight additional risk factors, such as extensive...

Cancer risk among patients with coal workers' pneumoconiosis in Taiwan: A nationwide population‐based study

This study is aimed to evaluate the cancer risk among patients with coal workers' pneumoconiosis (CWP) using a nationwide population-based dataset. Patients without previous cancer who had been diagnosed with CWP and followed-up for more than 1 year between 1997 and 2006 were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of cancers in CWP patients were calculated and compared to the cancer incidence in the general population. Risk factors for cancer development were also analyzed. After a median follow-up of 9.68 years, 954 cancers developed among 8,051 recruited CWP patients, with a follow-up of 69,398 person-years. The SIR for all cancers was 1.12 [95% confidence interval (CI) 1.04-1.18]. Males older than 80 years had a SIR of 1.27 (95% CI: 1.06-1.51). The SIRs of esophageal (1.76, 95% CI: 1.24-2.44), gastric (1.42, 95% CI: 1.13-1.76), liver and biliary tract (1.18, 95% CI: 1.01-1.37) and lung and mediastinal (1.45, 95% CI: 1.26-1.66) cancers were significantly higher in the CWP group than in the general population. Multivariate analysis showed that age ≥ 60 years [hazard ratio (HR) 1.70, 95% CI: 1.41-2.05), male gender (HR = 1.79, 95% CI: 1.44-2.23) and liver cirrhosis (HR = 3.99, 95% CI: 2.89-5.51) were significant predictors of cancer development in patients with CWP. We concluded that patients with CWP, especially elderly males, were at increased risk of cancer. Age, male gender and liver cirrhosis were independent risk factors for cancer development.

Current methods for preventing the development of cervical cancer in patients with papilloma viral infection

The article presents the results of recent studies of the role of human papillomavirus in potentiating cancer in the cervix. the authors describe methods for organizing efforts aimed at early diagnostics of cancer pathologies associated with papilloma viral infection. they describe aspects of the prevention of cervical cancer in Russia and abroad. they also disclose current screening strategies related to cancer pathologies of the cervix based on a combination of diagnostics methods.

Tumors in rheumatic diseases

Patients with systemic inflammatory rheumatic diseases (such as rheumatoid arthritis, lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, or Sjögren's syndrome) are at increased risk of cancer, including hematological malignancies (leukemias and lymphomas), as well as non-hematological cancers (e.g. lung, esophageal, prostate or ovarian cancer). This increased risk for cancer development in patients with rheumatic diseases is attributed to the immune (autoimmune) processes and the medical treatment. Due to the often similar symptoms and the occurrence of systemic paraneoplastic syndromes it is very important to evaluate the association between rheumatic diseases and cancer. This paper presents issues concerning the development of cancer in patients with rheumatic diseases and the risk of cancer associated with drugs used for the treatment of rheumatic diseases.

Comparative preclinical pharmacokinetics study of 3,3′-diindolylmethane formulations: is personalized treatment and targeted chemoprevention in the horizon?

Background3,3′-Diindolylmethane (DIM) is known as an agent of natural origin that provides protection against different cancers due to the broad spectrum of its biological activities in vivo. However, this substance has a very poor biodistribution and absorption in animal tissues. This preclinical trial was conducted to evaluate the pharmacokinetics and bioavailability of various DIM formulations in animal model.Materials and methodsThe pharmacokinetic parameters of one crystalline DIM formulation and one liquid DIM formulation (oil solution) compared to non-formulated crystalline DIM (control) were tested in 200 rats. The formulations were orally administered to animals by gavage at doses of 200 mg/kg per DIM (crystalline DIM formulation and non-formulated crystalline DIM) and 0.1 mg/kg per DIM (DIM in oil solution). DIM plasma elimination was measured using HPLC method; after that, the area under the curve (AUC), relative bioavailability, and absolute bioavailability were estimated for two formulations in relation to non-formulated crystalline DIM.Results and conclusionThe highest bioavailability was achieved by administering liquid DIM (oil solution), containing cod liver oil and polysorbate. The level of DIM in rat blood plasma was about fivefold higher, though the 2,000-fold lower dose was administered compared to crystalline DIM forms. The novel pharmacological DIM substance with high bioavailability may be considered as a promising targeted antitumor chemopreventive agent. It could be used to prevent breast and ovarian cancer development in patients with heterozygous inherited and sporadic BRCA1 gene mutations. Further preclinical and clinical trials are needed to prove this concept.