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Summary

Lung cancer is still the leading cancer-related cause of death with a high incidence rate in the whole world. Treatment options – surgery, radiotherapy, and chemotherapy, depending on the stage of the disease. During the last decade, many molecular alterations were discovered that led to impressive changes in treatment. Personalized approaches, including target therapies with specific inhibitor drugs, became a part of the standard therapies. This article reviews current molecular biomarkers used in clinical practice to treat lung cancer patients.

Abstract

The aim of the investigation presented in this paper was to develop a software-based assistant for the protein analysis workflow. The prior characterization of the unknown protein in two-dimensional electrophoresis gel images is performed according to the molecular weight and isoelectric point of each protein spot estimated from the gel image before further sequence analysis by mass spectrometry. The paper presents a method for automatic and robust identification of the protein standard band in a two-dimensional gel image. In addition, the method introduces the identification of the positions of the markers, prepared by using pre-selected proteins with known molecular mass. The robustness of the method was achieved by using special validation rules in the proposed original algorithms. In addition, a self-organizing map-based decision support algorithm is proposed, which takes Gabor coefficients as image features and searches for the differences in preselected vertical image bars. The experimental investigation proved the good performance of the new algorithms included into the proposed method. The detection of the protein standard markers works without modification of algorithm parameters on two-dimensional gel images obtained by using different staining and destaining procedures, which results in different average levels of intensity in the images.

Abstract

Background

Histological parameters of primary tumour and nodal metastases are prognostic factors for survival of operable colorectal (CRC) patients, but not predictive for response rate of systemic therapy. KRAS mutations in codons 12 and 13 were first recognized as a predictive factor for resistance to anti-EGFR monoclonal antibodies. Not all patients with wild-type KRAS (wtKRAS) respond to anti-EGFR antibody treatment. Additional mechanisms of resistance may activate mutations of the other main EGFR effectors pathway, such as other mutations in RAS gene, mutations in P13K and PTEN expression.

Patients and methods

In the prospective study prognostic and predictive impact of histological parameters of primary tumour, KRAS and BRAF mutations on overall survival (OS) and objective response (OR) rate of metastatic CRC (mCRC) patients treated with 1st line systemic therapy were analysed. We additionally retrospectively analysed other mutations in RAS genes and their impact on survival and time to progression.

Results

From November 2010 to December 2012, we enrolled 154 patients in the study, 95 men and 59 women. Mutations in KRAS gene and V600E BRAF gene were found in 42% and in 3% of patients, respectively. Median OS of the patients with T1, T2 and T3 tumour was 65.4 months (95% CI, 55.7–75.6) while in patients with T4 tumour, lymphangiosis, vascular and perineural invasion it has not been reached yet. Median OS of the patients with G1, G2 and G3 of tumour differentiation was 65.6 (95% CI, 53.7–77.5) and 25.3 months (95% CI, 16.6–34.1), respectively. Median OS of the patients with stage N0, N1 and N2 was 65.6 (95% CI, 56.4–74.8) and 58.0 months (95% CI, 21.9–94.2), respectively. Median OS of wtKRAS and mutated KRAS patients was 56.5 (95% CI, 48.2–64.9) and 58 months (95% CI, 52.6–63.4), respectively. Median OS of mutated codon 12 and codon 13 patients was 57 (95% CI, 50.9–64.4) and 44 months (95% CI, 40.1–48.4), respectively. Median OS of wtBRAF and of mutated BRAF patients was 59.2 (95% CI, 52.5–65.9) and 27.6 months (95% CI, 12.6–42.5), respectively. wtKRAS significantly affected the response to the first systemic therapy (p = 0.028), while other parameters did not affected it, p= 0.07. In 14 patients (17%), additional mutations in NRAS gene, codon 61 and codon 146 were found. Median OS of wtNRAS, codon 61 and 146 patients was 67.1 months (50.3–67.6) while median OS of mutated NRAS patients has not been reached yet (p = 0.072). Median time to progression of wtNRAS, codon 61 and 146 patients was 11.7 months (10.4–14.5) while median time to progression of mutated NRAS patients was 7.9 months (6.1–11.0), (p = 0.025).

Conclusions

Mutated BRAF, N2 and G3 of primary tumour were poor prognostic factors for OS in mCRC patients. wtKRAS significantly affected the response to the first line systemic therapy. Histological parameters included in the analysis and mutated BRAF did not affect significantly the efficacy of 1st line systemic therapy in mCRC patients.

.M., Bubendorf, L., Edelman, M.J., Marchetti, A., Mok, T., Novello, S., O'Byrne, K., Stahel, R., Peters, S. & Felip, E. (2014). Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer. Annals of Oncology, 25(9), 1681-1690. doi: 10.1093/annonc/mdu145 12. Leighl, N.B., Rekhtman, N., Biermann, W.A., Huang, J., Mino-Kenudson, M., Ramalingam, S.S., West, H., Whitlock, S. & Somerfield, M.R. (2014). Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma

Abstract

-Oxidative stress and antioxidant defence systems were assessed in a marine red alga Porphyra vietnamensis Tanaka et Pham-Hoang Ho, from India. Lipid peroxidation (LPX) and hydrogen peroxide (H2O2) were measured as oxidative stress markers. Antioxidant defences were measured as catalase (CAT), glutathione S-transferase (GST) and ascorbic acid (AsA), in order to understand their dissimilarity with respect to environmental conditions (pollution levels) from selective locations along the central west coast of India. Levels of LPX, H2O2, CAT and GST were significantly higher in samples collected from Dona Paula than in samples from Malvan and Kunkeshwar, while a lower concentration of AsA was found in samples from Dona Paula. Heavy metals such as Cd, Pb and Hg in higher concentrations in these areas than in other sites were also observed. Variation of oxidative stress indices in response to the accumulation of heavy metals within P. vietnamensis could be used as molecular biomarkers for the assessment and monitoring of environmental quality in ecologically sensitive marine habitats.

Abstract

Prostate adenocarcinoma, remaining among top most common cancers, is a heterogeneous group of tumors with a diverse morphological structure. Basing on the histological architecture of cancer tissue, individual cases can be classified into different therapeutic groups. Current diagnosis of prostate cancer brings many challenges. The major problem is the lack of effective and accessible diagnostic methods that would eliminate incidences of overdiagnosis and prevent unnecessary treatments of many patients. There are many efforts to determine favorable and unfavorable molecular prognostic factors. The basic marker currently used in this field is prostate-specific antigen (PSA). Increased level of PSA may suggest the presence of prostate cancer although its level is not specific for the disease and can be elevated also in certain benign hyperplastic or inflammatory conditions as well as after irritation or rectal examination. Clinical symptoms such as dysuria or hematuria are often uncharacteristic and benign prostatic diseases which cannot be confirmed on the basis of physical examination alone. Also, we often deal with the situation of false negative results of prostate needle biopsy, which require many tests to determine the final correct diagnosis. Moreover, prostate cancer can also be present in patients with non-elevated serum PSA level. Due to such difficulties, the search for new molecular markers that could be used for diagnostic purposes is underway. Evaluation of survivin level in prostate cancer tissue may serve as a new diagnostic indicator of prostate cancer progression. Other useful molecular biomarkers with good potential in prostate cancer diagnosis are AMACR (Alpha Methyl Acyl Coenzyme A Racemase), p-63 or Ki-67 or microRNAs present in body fluids.

Abstract

The morphological and biochemical modification of oviductal epithelial cells (OECs) belongs to the compound process responsible for proper oocytes transport and successful fertilization. However, the main mechanisms which regulated this process are still not entirely known. Moreover, the OECs metabolism, which may be identified as the “cellular activity” marker, is poorly recognized. In this study we investigated the fructose and mannose metabolic pathway in porcine OECs primary long-term cultured in vitro.

In our study, we employ a primary long term in vitro culture (IVC) and microarray approach (the Affymetrix microarray were used for analysis of transcriptomic profile of OECs) for expression levels analysis.

We found that from the whole analyzed transcriptome, 1537 genes were upregulated and 995 were down regulated after 7 days of culture, 1471 genes were upregulated and 1061 were downregulated after 15 days of culture and 1329 genes were upregulated and 1203 were downregulated after 30 days of culture. Moreover, the differential expression of SORD, FPGT, PFKFB4, TPI1, MPI, ALDOC, HK2 and PFKFB3 at 24 hours, 7 day, 15 day and 30 day, was also observed.

We suggested that fructose and mannose metabolism may be important molecular bio-marker of porcine OECs capability in in vitro model. The metabolic profile is significantly accompanied by cells proliferation in vitro. The transcriptomic profile of SORD, FPGT, PFKFB4, TPI1, MPI, ALDOC, HK2 and PFKFB3 expression may be identified as “fingerprint” of fructose and mannose metabolism in OECs as well as involved in cellular in vitro developmental capacity in pigs.

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