Krebswissenschaft und -therapie

Background: In TP53 gene, Arg72Pro polymorphism has been suggested to be associated with genetically determined susceptibility in various types of cancers including brain tumors. Our objective was to investigate the possible association between TP53 Arg72Pro polymorphism with brain tumor susceptibility and to examine its correlation with the clinico-pathologic variables of tumor cases for oncologic prognosis of patients.

Materials and methods: The TP53 Arg72Pro genotypes were determined by Polymerase Chain Reaction- Based Restriction Fragment Length Polymorphism (PCR-RFLP) analysis in 90 age and gender matched brain tumor cases and 130 healthy controls.

Results: We found significant difference in the frequency of Pro allele as 0.47 in cases versus 0.37 in controls (p<0.05).Though the distribution of the TP53, 72Pro genotypes in patients were higher (24.4%) compared with the control group (17.7%) with an odds ratio of 1.9 but no statistical difference was found (p>0.05). Proline related allele/genotype (GC) was significantly found associated in high grade malignant brain tumors, neuroepithelial tumors (p<0.05). Overall and disease-free survivals were calculated but no significant statistical difference was observed between the two groups (p>0.05).

Conclusion: Though overall distribution did not reveal significant association in TP53 Arg72Pro polymorphism among cases and controls but proline related genotype was found associated with susceptibility to the disease pathology.

Objective: Lactic acid bacteria such as Lactobacillus fermentum, have shown to increase the levels of fecal short chain fatty acids known with its beneficial role in colonic health and were found to produce anti-carcinogenic compounds, suggesting a potential in colorectal cancer prevention. The aim of this study is to characterize the metabolic and anti-cancer features of L. fermentum NCIMB 5221 compared to two other Lactobacillus species.

Methods: A free fatty acid (FFA) profile was determined and the anti-proliferative and apoptotic effects of bacterial cell free extracts were investigated. The effect on the growth of colon cancer cells compared to nonneoplastic colon cells was determined. The production of different SCFAs by the probiotic bacteria and the efficacy of their composition were analyzed.

Results: The FFA profile of L. fermentum is distinctive FFA profile (~ 368 MAE, 16 h, p < 0.01) compared to L. acidophilus ATCC 314 and L. rhamnosus ATCC 53103. L. fermentum extracts significantly inhibited cancer cell growth up to ~ 40% and induced apoptosis up to ~ 30% in SW-480 colon cancer cells (24 h, p < 0.05) compared to the untreated cells. However, L. fermentum did not inhibit CRL-1831 non-neoplastic colon cell growth but had a significant anti-proliferative effect against Caco-2 cancer cells (~ 60%, 72 h, p < 0.001) compared to control, which was related to the higher levels of SCFAs produced (~ 377 mg/L). Similar concentrations of SCFA formulations (that correspond to what was produced by L. fermentum) have shown the same inhibitory effect on Caco-2 cells.

Conclusion: L. fermentum NCIMB 5221 was more potent in suppressing colon cancer cells and promoting normal epithelial colon cell growth by the production of SCFAs and could be considered as biotherapeutic agent for the support of colonic health and the prevention of colorectal cancer.

Background: We investigated the effects of the frequently polymorphic high iron gene (HFE), on tumor growth in a novel mouse model. We hypothesized that host mutations in the HFE protein modify tumor progression.

Methods: C57BL/6 mice possessing either H67D/H67D or WT/WT HFE genotype, aged 18 months, were injected subcutaneously with 4x106 cells of the B16F10 mouse melanoma cell line. After 2 weeks, mice were sacrificed and the tumors and plasma were collected. Animal methods were approved by our IACUC, (04-166). Tumors were analyzed by RT-PCR. In parallel, bone marrow derived macrophages were cultured to determine how B16F10 cell cultures react to conditioned media from macrophages of each genotype. ELISAs were performed for ferroportin, ferritin, secreted cytokine and chemokine content of macrophage media. Results: H67D mice had significantly smaller tumors (t-test, P = 0.02) after two weeks. Exploratory qRT-PCR analysis of tumors revealed that the H67D host may suppress angiogenesis and growth. In culture, macrophages derived from H67D mice secrete higher levels of monocyte chemoattractant protein 1 (MCP1), suggesting a change in chemotactic signaling (p = 0.02). When conditioned media from the H67D macrophages were placed onto B16F10 cells in culture there was significantly less growth compared to conditioned media from WT macrophages (p < 0.01 MTT, p < 0.01 BrdU). In macrophage cell lysates, H67D is associated with lower levels of Ferroportin (p = 0.03). Conclusions: Macrophages from H67D mice do not support tumor cell proliferation as well as WT controls. Our data reveal the importance of HFE genotype on tumor growth that may be related to macrophage function.

The present study was aimed to investigate the chemopreventive potential of Silibinin (SIB) against N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma (HCC) in wistar rats. Thirty experimental animals were subjected to partial hepatectomy (PH) and after 24 hours of stabilization period a single dose of NDEA (100 mg/kg b.w., i.p) was administered to each animal followed by CCl4 (1 ml/kg b.w., s.c.). The effect of SIB (25 and 50 mg/kg/day, i.p.) on NDEA-induced HCC was determined after 2 weeks of treatment (6th to 8th week after PH, in the promotional stage of tumor development). NDEA treatment to rats resulted in significant decrease in body weight and increase in liver weight along with levels of transaminases, γ-glutamyl transferase, lipoprotein, glycoproteins. Hepatic and serum malondialdehyde content, enzymatic and non-enzymatic antioxidant levels were also altered in HCC bearing animals without treatment. Bio-structural components (such as amide bands of proteins, symmetric phosphate stretching of nucleic acids, methylene chains in membrane lipids, methyl to methylene ratio of carbohydrates and proteins etc.) were marked in NDEA-treated groups of animals by analysing changes in the position and intensities of the peaks in Fourier transform infrared spectroscopy (FTIR). Immunohistochemical staining of Ki67 and histopathological analysis were also carried out in order to support the study. SIB treatment could attenuate NDEA-induced hepatocarcinogenesis by improving the biochemical and bio-structural changes of the hepatic tissue near normal levels in a dose dependent manner. Taken together, this study reveals that SIB may have potential as a multi-functional drug candidate for cancer therapy.

In last years, many phase III studies have addressed the role of chemotherapy or chemo/biotherapy in metastatic colorectal cancer (mCRC); most of these studies planned their treatment to be continued until disease progression or intolerable toxicity with the aim to obtain a long-term control of the cancer. However, the real duration of this approach might be significantly lower than planned. We made a survey to describe the real duration of chemotherapy in published phase III trials from January 2008 to December 2014. Twenty relevant publications were selected for a total of 48 treatment arms and of 24.475 patients. Median duration of chemotherapy in first-line studies ranged from 4,8 to 7,8 months; in second line from 2,4 to 5,2 months. Most common reasons of discontinuation were: progressive disease (PD), adverse events (AE) and patient request (PR). From 11.0% to 45.0% of patients discontinue treatment for toxicity or their request independently from the efficacy. PR was the third cause ranging from 4,6% to 26,0% of patients; in some studies, it overcame the AE-related withdrawals. Causes of PR for therapy discontinuation should be explored and analyzed to reduce the proportion of withdrawals in phase III studies.

Thyroid cancer is the most prevalent endocrine malignancy affecting 213,000 people every year worldwide. There are many types of thyroid disorders including hyperthyroidism, hypothyroidism, Goitre, Hashimoto’s thyroiditis. The ocean of information that is available with respect to molecular markers related to Thyroid disorders and cancer is scattered in literature. Thyroid Cancer and Disorder Gene Database (TCGDB) is a compendium of genes and miRNAs experimentally known to be involved in thyroid cancer and disorders. The current release of TCGDB houses a collection of 250 genes and 120 unique miRNAs compiled by manual screening of numerous research articles. The literature references have been provided for each entry to establish its association with thyroid cancer and disorders. TCGDB provides information on miRNA in body fluids which can be used as potential biomarkers for diagnosis of thyroid cancer and disorders. We have also analysed the overlap of thyroid cancer related miRNAs with other type of cancers. The database provides various browse and search options for users to quickly extract required information. TCGDB will help in prioritizing, systematic testing and comparative analysis of candidate biomarkers for cancer diagnosis. It is freely accessible at http://www.juit.ac.in/attachments/tcgdb/index.php

Metastases are the most common neoplasm of the brain. When these occur in the brainstem, prognosis is poor and treatment options are limited. However, stereotactic radiosurgery has been investigated as a management tool for brainstem metastases. The aim of this review is to gather and summarize data related to the safety and efficacy of stereotactic radiosurgery for the treatment of brainstem metastases. To identify trials for inclusion in this review, a PubMed search using the keywords “stereotactic radiosurgery” and “brainstem metastases” was performed. With this method, we selected 21 series published between 1999 and 2014. Median survival times for these studies averaged 8.3 months (range: 3-16.8 months). Control of systemic disease and performance status were identified as important predictors of survival time. Adjuvant whole-brain radiation therapy was not shown to increase survival. The studies reviewed here report adverse radiation effects at an average rate of 6.7% (range: 0-27%). Stereotactic radiosurgery provides effective local tumor control and may increase survival time for patients with brainstem metastases. Further study is needed to establish dosage guidelines for maximal benefit as well as to evaluate the efficacy of radiosurgery in symptom management.

In the present report we’re going to describe a rare case of synchronous lung adenocarcinoma and non- Hodgkin B-cell lymphoma in both hilar and mediastinal lymphnodes. The primitive pulmonary epithelial neoplasm was effectively managed with a right upper lobectomy and an adjuvant chemotherapy, while the indolent lymphoproliferative disorder did not require any treatment. The 24-month follow up did not show relapses.