Tumor and immunity

System of organism defense is an important complex of interrelated cellular, molecular, genetic, and other components, which regulate homeostasis of host. Experimental and clinical data show that immune system functions are significant, but also a complicated question in cancer development. It is very important to investigate and understood how immune system coordinates the response to cancer cells. Our understanding about innate and adaptive immunity functions and interaction with transformed cells is constantly changing. Different responses of these system components can promote, reduce, or inhibit tumor development. It is established that malignant cells develop into invasive cancer with interaction with tumor microenvironment, which is influenced by inflammation. Clinical and experimental studies have revealed the link between inflammation and cancer risk. Many cancers develop in the sites of inflammation. Activation of humoral and cellular immunity may predispose to neoplastic or cancer development. Despite the scientific progress, understanding of the immune system mechanisms responding to malignance remains insufficient

Chirurginio gydymo įtaka sergančiųjų imuninei sistemai ir pacientų lytis

Vilniaus universiteto Onkologijos institutas, Santariškių g. 1, LT-08660 Vilnius El. paštas: [email protected] Straipsnyje apžvelgti tyrimai, susiję su chirurginio gydymo poveikiu vėžiu sergančių ligonių imuninei sistemai. Operacija sutrikdo imuninės sistemos funkcijas ir gali skatinti ligos progresavimą. Nustatyta skirtinga imuninės sistemos reakcija į traumą ar kitokius pažeidimus priklausomai nuo lyties (vyrams imunosupresija yra stipresnė nei moterims). Svarbu išsiaiškinti, ar po chirurginės intervencijos nevienodos vyrų ir moterų imuninės sistemos funkcijos gali turėti įtakos piktybinės ligos eigai. Tyrimai rodo, kad atsakas gali būti susijęs su lytiniais hormonais. Kol kas yra mažai informacijos apie sergančių vėžiu ligonių imuninės sistemos veiklos pokyčius pooperaciniu laikotarpiu priklausomai nuo lyties, o sutrikdytų šios sistemos funkcijų korekcija po operacijos gali padėti numatyti veiksmingesnes gydymo strategijas atsižvelgiant į ligonio lytį. Reikšminiai žodžiai: operacija, imunitetas, vėžys, lytis. The influence of surgical treatment on cancer patients immune system and according to gender Birutė Kazbarienė Institute of Oncology, Vilnius University, Santariškių Str. 1, LT-08660 Vilnius, Lithuania E-mail: [email protected] This article focuses on the effect of surgical stress on cancer patients immune system. Surgery induces dysfunction of the immune system and may promote remnant cancer cell growth and metastasis. Difference of the immune system functions between females and males is seen in the response to injury (immunosuppression is more expressed in men than in women). It is important to determine whether or not different immune response in men and women may influence cancer development after surgery. Researches suggest that response may be linked with various sex hormones. For the present time there isn’t enough information about immune system functions of cancer patients depending on their gender in perioperative period. Therefore future investigations are necessary because restore of immune system disturbance may provide the better opportunity to choose treatment strategy in dependence of the cancer patients gender. Keywords: surgery, immunity, cancer, gende

Significance of blood serum catalase activity and malondialdehyde level for survival prognosis of ovarian cancer patients

Background and objective: Several markers were found to be potential prognostic factors in ovarian cancer. Among markers resembling systemic changes in the host\u27s organism are markers of the oxidative stress. In this study we attempted to analyze the oxidant and antioxidant parameters of ovarian cancer patients.Materials and methods: A total of 42 patients with newly diagnosed stages I–IV primary ovary cancer were examined. Level of malondialdehyde (MDA) and catalytic activity catalase (CAT) were determined spectrophotometrically.Results: Significantly lower CAT (28.2 ± 15.5 vs. 36.1 ± 14.6 nmol/L/min, P = 0.019) activity and higher MDA levels (8.7 ± 3.0 vs. 6.7 ± 2.7 nmol/L, P = 0.002) were observed in cancer patients compared with healthy volunteers. Both variables were not confirmed as prognostic factors according to Kaplan–Meier survival estimates.Conclusions: MDA and CAT demonstrate oxidative stress in cancer patients: CAT activity was significantly lower and MDA levels higher in cancer patients compared to healthy controls. These variables were not confirmed to be prognostic factors in ovarian cancer, possibly due to small size of the study group

E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma.

Melanomas are highly proliferative and invasive, and are most frequently metastatic. Despite many advances in cancer treatment over the last several decades, the prognosis for patients with advanced melanoma remains poor. New treatment methods and strategies are necessary. The main hallmark of cancer is uncontrolled cellular proliferation with alterations in the expression of proteins. Ubiquitin and ubiquitin-related proteins posttranslationally modify proteins and thereby alter their functions. The ubiquitination process is involved in various physiological responses, including cell growth, cell death, and DNA damage repair. E3 ligases, the most specific enzymes of ubiquitination system, participate in the turnover of many key regulatory proteins and in the development of cancer. E3 ligases are of interest as drug targets for their ability to regulate proteins stability and functions. Compared to the general proteasome inhibitor bortezomib, which blocks the entire protein degradation, drugs that target a particular E3 ligase are expected to have better selectivity with less associated toxicity. Components of different E3 ligases complexes (FBW7, MDM2, RBX1/ROC1, RBX2/ROC2, cullins and many others) are known as oncogenes or tumor suppressors in melanomagenesis. These proteins participate in regulation of different cellular pathways and such important proteins in cancer development as p53 and Notch. In this review we summarized published data on the role of known E3 ligases in the development of melanoma and discuss the inhibitors of E3 ligases as a novel approach for the treatment of malignant melanomas

The significance of reduced glutathione and glutathione S-transferase during chemoradiotherapy of locally advanced cervical cancer

Background and objective: To determine changes in reduced glutathione (GSH) and glutathione S-transferase (GST) during neoadjuvant chemotherapy followed by concurrent chemoradiation for patients with stage IIB–IIIB cervical cancer, and to evaluate their significance to the efficacy of the treatment.Materials and methods: According to the prospective phase II study protocol, 36 patients with stage IIB–IIIB cervical cancer were enrolled. A short course of intensive weekly neoadjuvant cisplatin and gemcitabine chemotherapy followed by concurrent weekly cisplatin and gemcitabine-based chemoradiation was administered. Blood samples for GSH, GST analysis were collected and analyzed before the start of the treatment, after neoadjuvant chemotherapy, and after the end of the chemoradiation.Results: A statistically significant increase in the concentration of GSH after neoadjuvant chemotherapy was identified. After chemoradiation, values of this rate significantly decreased in contrast with GSH concentration after neoadjuvant chemotherapy in cases of stage IIB, regional metastases negative patients group, patients with a positive response to treatment, and patients who had no progression of the disease during the first 2 years after treatment. Statistically significant changes in GST during the treatment were not identified; the GST concentration after chemoradiation showed a statistically significant difference in GST con- centrations in terms of the progression of the disease and disease without progression.Conclusions: The results suggest that changes in the concentration of GSH during the treatment of locally advanced cervical cancer might be important for the prediction of the efficacy of the treatment. Statistically significant changes in GST concentration levels during the treatment were not observed

The association between the NOTCH signaling pathway and gynaecological malignancies

Background. The body’s cell behaviour is controlled by various signalling pathways, one of which is NOTCH. It has been found that a partial loss of the NOTCH function or abnormal strengthening of NOTCH signalling are related to various human diseases and developmental disorders. Materials and methods. PubMed was the main source of information for this paper. Results. The paper overviews the association between oncologic diseases and the participants of the NOTCH signalling pathway. In cancerogenesis, the NOTCH signalling pathway can act as a tumour suppressor or an oncogene. The mechanisms of such an effect are yet unknown. The NOTCH signalling pathway is an object of active research because its modulation by pharmacological and genetic approaches could be helpful in discovering new treatment methods of tumours. In this review more attention is paid to gynaecological malignancies, especially to uterine cancer. Conclusions. The findings of recently published studies show that the NOTCH signalling pathway is definitely important for the development of uterine cancer, therefore its components can be potential prognostic biomarkers and molecular therapeutic targets. However, further studies in this field are needed in order to clarify the role of the components of the NOTCH signalling pathway and their interaction with participants of other signalling pathways, which can be important in the development and progression of uterine cancer as well

NOTCH1, NOTCH3, NOTCH4, and JAG2 protein levels in human endometrial cancer

Background and objective: Notch signaling is a conserved developmental pathway, which plays an important role in the regulation of cell proliferation, differentiation and death. Deregulation of Notch pathway has been connected with the carcinogenesis in a variety of cancers. The aim of this study was to investigate the level of the Notch signaling pathway proteins (NOTCH1, 3, 4 and JAG2) in the samples from human endometrial cancer. Materials and methods: The amount of the Notch receptors NOTCH1, 3, 4 and ligand JAG2 protein was determined by Western blot analysis in the samples from stage I endometrial cancer and adjacent nontumor endometrial tissue of 22 patients. Results: The level of NOTCH4 receptor was 1.7 times lower in stage I endometrial cancer as compared with the healthy tissue of the same patients (P = 0.04). The protein level of ligand JAG2 was significantly reduced by 2.5 times in stage IB endometrial adenocarcinoma samples (P = 0.01). It was reduced in the majority of stage IB adenocarcinomas. There were no significant changes in the protein amount of NOTCH1 and NOTCH3 receptors comparing stage I endometrial adenocarcinoma and healthy tissues. Conclusions: The reduced amount of NOTCH4 and JAG2 proteins and the decreased level of mRNA coding Notch proteins, as reported in our previous studies, supports the notion that Notch pathway has rather tumor-suppressive than oncogenic role in human endometrial cancer cells. It suggests that Notch pathway activation is a potential therapeutic target