Despite an observed decrease in the incidence of gastric cancer, it still remains an important clinical problem. It is the fourth most common cancer in the world and the second cause of death in cancer patients. The quality of lymphadenectomy procedure and the number of analysed lymph nodes are both important factors influencing the treatment of the patient. The aim of the study was to compare the lymph node ratio staging system with the 6th and 7th edition of the TNM classification. Material and methods. A group consisting of 493 patients who underwent surgery in 1998–2010 due to gastric cancer was used to compare the staging systems. Following statistical analysis, the following cut-off points were adopted for the lymph node ratio for the purpose of comparison: 0, from 0.05 to 0.3, from 0.3 to 0.5 and over 0.5. Subsequently the homogeneity (using chi-square test for linear trend) and the predictive value of the different classifications (using Akaike information criterion) were assessed in order to compare the lymph node ratio staging system with the 6th and 7th edition of the TNM classification. Results. The lymph node ratio classification has a higher discriminatory value than the TNM classifications (higher linear trend result). What is more, the lymph node ratio classification (LNR) had a lower Akaike information criterion value, which means that it has a higher prognostic value than the other classifications. ROC curves and the area under the curve (AUC) were utilised for the analysis of predictive value of the different classifications in patients with gastric cancer. Conclusion. One may conclude, therefore, that the lymph node ratio staging system is the best classification of the lymphatic system in the presented group of patients.
Presence of free gastric cancer cells in the peritoneal cavity of patients who underwent surgical treatment for gastric cancer is a negative prognostic factor and caused rapid disease recurrence, manifested as peritoneal metastases. Positive peritoneal cytology despite lack of visible peritoneal metastases was regarded as M1 class in the TNM classification (7th edition) in 2010. The aim of the study was to analyze factors associated with positive peritoneal cytology and identify groups of patients in whom diagnostic laparoscopy plus peritoneal lavage in the diagnostic process could affect therapeutic decisions. Material and methods. The study enrolled patients with gastric cancer who underwent surgical treatment at the Department of Surgery, Wielkopolskie Oncology Center in Poznań. During the laparotomy, after opening of the peritoneal cavity, 200 ml of physiological saline at 37°C was administered in the tumor region. After this fluid was mixed, 100 ml of lavage fluid was collected. This fluid was subsequently spun many times to obtain sediment for cytology and immunohistochemistry investigation using anti-BerEp-4, CK 7/20, and B72.3. Results of peritoneal cytology were analyzed jointly with clinical factors – patient’s age, sex and pathology factors – tumor invasion, involvement of lymph nodes, histological grade, histological type according to Lauren and localization of the cancer in the stomach. Results. Analysis of the peritoneal fluid for presence of free cancer cells was done in 51 patients. Positive peritoneal cytology was found in 12 (23.5%) patients. In the group of patients with positive cytology, all patients had T3/T4 tumors and all were found to have lymph node metastases, while G3 cancer was found in 83.3% of patients. In patients with positive cytology, diffuse gastric cancer according to Lauren predominated (9 of 12 patients, 75%), while in patients with negative cytology – intestinal type (20 of 39 patients, 51.2%). In the group of patients with positive histology, the whole stomach was involved by the cancer process in 7 of 12 patients (58.3%), while in the group with negative histology, in 29 of 39 patients the tumor was located in the gastric body and prepyloric part (74.4%). Conclusions. Based on this study we can conclude that determinants of positive peritoneal cytology include: tumor stage T3/T4, N+, G3, cancer located in the whole stomach, diffuse histological type according to Lauren.
We report a case of patient with stage IIIb gastric cancer qualified for laparoscopy - assisted gastrectomy and our first impressions about this procedure. Total gastrectomy with complete omentectomy and extended lymphadenectomy (D2) was performed laparoscopically. The intestinal continuity was restored in a Roux-en-Y mode extracorporeally through the abdominal access system. The orogastric tube with anvil of the circular stapler was transorally introduced into the esophagus. Subsequently, intracorporeal stapling esophagojejunostomy was performed. There were no complications after the operation and the patient was discharged in good shape. Oncological radicality was sufficient and patient has undergone chemotherapy treatment.
The study presented a patient with asymptomatic gastric cancer, in whom the first symptom was metastasis to the brain. The patient was initially diagnosed by a neurologist and subject to surgical intervention in the area of residence, where he underwent craniotomy with the excision of the metastatic lesions located in the occipital lobe. The histopathological examination revealed the presence of adenocarcinoma metastases. Following complex diagnostics the patient was diagnosed with cardial carcinoma, being subject to cerebral radiotherapy and chemotherapy. The patient was then referred to surgery at the Wielkopolska Cancer Center in Poznań. After final exclusion of disease dissemination (by means of PET-CT) the patient underwent total gastrectomy with D2 lymphadenectomy, and gastrointestinal tract reconstruction by means of the Roux-en-Y method. The histopathological examination result was as follows: tubular-papillary G2 adenocarcinoma (intestinal type), pT2 pN0 (23 evaluated lymph nodes without cancer metastasis), vascular neoplastic emboli, and positive HER2 protein expression. After surgery the patient was subject to adjuvant chemotherapy. Control brain CT examinations revealed the presence of 4 recurrent metastatic lesions-the patient was disqualified from stereotactic radiation therapy and was subject to palliative chemotherapy. The discussion presented the problem of treating patients with stage IV gastric cancer, including current management guidelines, as well as literature review concerning the treatment of patients with diagnosed gastric cancer and brain metastases.
Effective treatment is the primary objective of surgeon in the treatment of advanced gastric cancer. Poor prognosis and significant advancement of gastric cancer at the time of diagnosis are decisive factors for the only possible surgical management method being palliative procedures.The aim of the study was the evaluation of the value of palliative resection procedures in patients with advanced gastric cancer.Material and methods. The subject in the study was a group of 105 patients with gastric adenocarcinoma at stage 4 of advancement, in whom curative treatment was not possible. The group constituted 44.5% of patients operated on due to gastric cancer at the Department of General and Oncological Surgery, PUM, in the years 1998-2009. The patients were divided into two groups: the first one comprised 44 patients post palliative resections, the second - 61 patients post non-resection procedures. The subject of analysis were early and late treatment results post palliative resections, and they were compared with the treatment results post non-resection procedures.Results. Palliative resections were performed in 44 patients (19 females and 25 males), while in 61 patients (38 males and 23 females) non-resection procedures were performed. Postoperative complications were observed in 25% of patients in the group post palliative resections and in 11.5% in the group of patients without the resection of primary focus. In-hospital mortality stood at 4.5% in the group post palliative resections and 4.8% in the group post non-resection procedures. The percentage of 1-year and 4-year survival post palliative resections stood at 43% and 8.8%, respectively. In the group without the resection of primary focus, 16% survived 1 year and nobody survived 2 years. Conclusions. Palliative resections improve the survival of patients with incurable gastric cancer and should be considered if only the loco-regional conditions are favourable.
Most patients diagnosed with gastrointestinal carcinomas are older people. The above-mentioned fact may lead to an erroneous finding that the problem does not concern patients aged between 20 and 30 years. Unfortunately, this assumption is often the reason for late diagnosis and delayed treatment of these malignancies. The study presented an example of three patients subject to surgical management of gastrointestinal carcinomas at the II Department of General and Gastroenterological Surgery, Medical University in Białystok.
The aim of the study was to assess angiogenesis markers - endostatin and endothelial growth factor (EGF) as markers of detection of gastric carcinoma.Material and methods. The study involved 20 patients with colorectal cancer (10 women, 10 men) aged 35 - 75 years, mean age = 55 years ± 11.2 who referred to the 2nd Department of General Surgery, Medical University in Lublin between June 2008 and June 2009. The control group comprised 10 volunteers (6 women, 4 men) who underwent upper gastrointestinal (GI) endoscopy due to the reflux disease and in whom gastric cancer was not diagnosed.Results. The mean endostatin concentration in controls was 5.21 ng/mL ± 1.37. Mean concentrations in patients with gastric cancer were higher than those in controls - 5.91 ng/mL ± 1.5. The difference was not statistically significant (p= 0.714). The EGF concentration in the control group was 28.19 pg/mL ± 12.94. EGF concentrations in patients with gastric cancer were higher compared to the control group - 28.8 pg/mL ± 12.63. The difference was not statistically significant (p= 0.85). The mean concentration of endostatin before the operation was 5.91 ng/mL ± 1.5 and after surgery was 5.33 ng/mL ± 2.01, the difference was not statistically significant.Conclusions. Blood endostatin and EGF quantitative determinations probably is not useful for detection of gastric carcinoma and effectiveness of treatment.
The only proven, effective therapy in case of the gastric cancers is surgery.The aim of the study. The most common procedure which is made in such a situation is total resection of the stomach. In our publication we would like to present and to recommend a very rare made type of the reconstructive procedures after total gastrectomy, which is called "double tract reconstruction" (DTR). This type of reconstruction is occasionally made mainly in Japan.Material and methods. Double tract reconstruction has been made in 2nd Department of General and Gastroenterological Surgery since 2000. Till today 75 patients were treated with this method.Results. The frequency of complications after double tract reconstruction was occasional, and there were no differences between this procedure and Roux-en-Y method of the reconstruction. There were no differences in the time of the operation between this two methods. The most important advantage of this method is that duodenal passage is extant. Because of that the endoscopic examination of papilla Vateri can be made.Conclusions. We would like to recommend this method as an alternative to Roux-en-Y procedure because of its simplicity and safeness.
Background: Helicobacter pylori (Hp) is classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen. Its influence on the carcinogenesis of gastric cancer has been confirmed in many research studies. The conclusion is obvious - early detection and eradication of Hp can prevent the development of the disease. Methods: The objective of the study was to analyze the clinical and practical value of Carbon-13 urea breath test (UBT) in patients hospitalized due to pain complaints in the upper abdomen and dyspeptic symptoms. Fifty patients were enrolled in the study. Each patient underwent urea breath test according to the instruction included by the producer. Thereafter, each patient included in the study group was subjected to endoscopy of the upper gastrointestinal tract with the biopsy of the mucosa to determine the urease activity with rapid urease test (RUT). Results: In the study group, 14 patients (28%) achieved a positive urease test result which was confirmed in RUT. Four (8%) patients, despite a positive breath test, did not have a positive result in urease activity test from gastric mucosa. In 2 cases (4%) despite negative result of UBT, urease activity was confirmed in gastroscopic sections. The remaining 30 patients (60%) had a negative result in both studies. Conclusions: The limited availability of the gold standard for diagnostics of upper gastrointestinal tract diseases (gastroscopy) is the basis for the search for new methods of detection of Helicobacter pylori infections. The urea breath test is a method of high sensitivity and specificity. The positive result of urea breath test may be the basis for inclusion of eradication therapy.
The occurrence of synchronous tumors of the gastrointestinal tract is rarely observed in general surgery, diagnosis is frequently incidental, often intraoperatively. The aim of this study was to present a case of a 50 year-old male patient admitted to the Department of Gastroenterology, University Hospital in Białystok, due to abdominal pain, significant weakness and excretion of tarry stools. Imaging diagnostics revealed the presence of a large gastric tumor (histopathological type - adenocarcinoma), and single metastasis to the liver. The patient was qualified for total gastrectomy. Surgery was performed at the 1st Department of General and Endocrinological Surgery, University Hospital in Białystok. Rectal cancer, which was observed during the operation was removed simultaneously.
Exact pretherapeutic staging is considered to be essential for decision-making in the therapeutic algorithm of gastric cancer.The aim of the study was to characterize the role and value of EUS in the diagnostic and therapeutic management of gastric cancer in daily surgical practice.Material and methods. Thousand one hundred thirty nine patients with primary gastric cancer from 80 hospitals of each profile of care were enrolled in this systematic clinical prospective multicenter observational study over a time period of 12 months. The characteristics of the diagnostic management, in particular, of EUS were documented. The preoperative EUS findings were compared with the T stage (T1 to T4) and the N category (N+ or N-) revealed by the histopathologic investigation of the surgical specimen. By the mean of X2 test, the impact of EUS on the therapeutic decision-making was determined.Results. Pretherapeutic EUS was only performed in 27.4% (n=312) of all patients. Overall, the diagnostic accuracy for the T stage was 42.6% in average. The subgroup analysis showed the following results: T1, 31.5%; T2, 42.6%; T3, 65.2%; T4, 17.6%. The correct predictive value of the N category was 71.3% reaching a sensitivity of 69.7% and a specificity of 73.3%. Overstaging was observed in 45.8%, understaging in only 10.8%. Additional diagnostic information by EUS was only provided in 4.7% of subjects.Conclusions. The present study indicates the variability, limited reliability and only moderate acceptance of EUS in diagnosing gastric cancer in daily practice. In particular, the prediction of the T stage does not reach the data reported in the literature, which were mostly achieved in specific EUS studies.
Despite the growing understanding of the pathophysiological processes in the perioperative period and significant advancements in surgical techniques, operative treatment for gastric cancer remains a challenge for surgeons, especially because the primary procedure of total or nearly total gastrectomy must at times be extended by the resection of other organs. The aim of the study was to asses the influence of concomitant splenectomy in patients undergoing curative surgery for gastric cancer on postoperative complications. Material and methods. The study population consisted of 258 patients who underwent surgical treatment for gastric cancer with the intention to treat. The study assessed the influence of extending the surgical intervention by splenectomy on postoperative complications, both general and surgical, including the most severe of these, i.e. oesophago-gastric anastomotic leakage, duodenal stump leakage and peritoneal fluid infections. Results. Among the 258 gastric cancer patients receiving curative surgical treatment, the most common simultaneous intervention was splenectomy: 42/258 (16.3%), which was also accompanied by partial pancreatectomy in 8 cases. The number of surgical postoperative complications, major and minor, was similar in both subgroups: with and without splenectomy. Minor general complications, such as pyrexia with no clinically apparent reason, atelectasis, pneumonia and pleural effusion were statistically significantly more common in the subgroup with splenectomy (p=0.0001). Conclusion. Splenectomy performed concomitantly with gastrectomy for gastric cancer increases the risk of minor general complications. However, it does not increase the risk of severe surgical complications, such as oesophago-intestinal anastomotic leakage and does not increase the risk of death
Introduction. Gastric cancer is malignant cancer, which is generated in the internal layers of the stomach. This type of cancer is often asymptomatic. There is a higher incidence of gastric cancer in patients over 50 years of age , especially in men. Aim. The aim of this study was to analyse selected aspects of nursing care in patients with gastric cancer. Material and methods. Analysis of available literature related to clinical aspects and nursing care in patients with gastric cancer and the activities of mapping medical diagnosis together with nursing care with the use of ICNP® dictionary. Results. The use of ICNP® classification allows to reflect patient's health situation in patients with gastric cancer and to plan medical care based on uniform professional terminology.
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Wstęp. Rak żołądka jest nowotworem złośliwym, który wywodzi się z komórek warstwy wewnętrznej narządu. Cechuje się długim okresem bezobjawowym. Zapadalność na raka żołądka zwiększa się po 50 roku życia, szczególnie w populacji mężczyzn. Cel. Celem pracy była analiza wybranych aspektów opieki pielęgniarskiej realizowanej wobec pacjenta w przebiegu raka żołądka. Materiały i metody. W pracy zastosowano metodę analizy piśmiennictwa poświęconego zagadnieniom klinicznym i opiece nad chorym z rakiem żołądka oraz mapowanie diagnoz i interwencji pielęgniarskich przy użyciu słownika ICNP®. Wyniki i wnioski. Zastosowanie klasyfikacji ICNP® umożliwia odzwierciedlenie sytuacji zdrowotnej pacjenta w przebiegu raka żołądka oraz planowanie założeń opieki pielęgniarskiej w oparciu o ujednoliconą terminologię zawodową.
The aim of the study was to analyze epidemiologic parameters, treatment-related data and prognostic factors in the management of gastric cancer patients of a university surgical center under conditions of routine clinical care before the onset of the era of multimodal therapies. By analyzing our data in relation with multi-center quality assurance trials [German Gastric Cancer Study - GGCS (1992) and East German Gastric Cancer Study - EGGCS (2004)] we aimed at providing an instrument of internal quality control at our institution as well as a base for comparison with future analyses taking into account the implementation of evolving (multimodal) therapies and their influence on treatment results.Material and methods. Retrospective analysis of prospectively gathered data of gastric cancer patients treated at a single institution during a defined 10-year time period with multivariate analysis of risk factors for early postoperative outcome.Results. From 04/01/1993 through 03/31/2003, a total of 328 gastric cancer patients were treated. In comparison with the EGGCS cohort there was a larger proportion of patients with locally advanced and proximally located tumors. 272 patients (82.9%) underwent surgery with curative intent; in 88.4% of these an R0 resection was achieved (EGGCS/GGCS: 82.5%/71.5%). 68.2% of patients underwent preoperative endoluminal ultrasound (EUS) (EGGCS: 27.4%); the proportion of patients undergoing EUS increased over the study period. Diagnostic accuracy of EUS for T stage was 50.6% (EGGCS: 42.6%). 77.2% of operated patients with curative intent underwent gastrectomy (EGGCS/GGCS: 79.8%/71.1%). Anastomotic leaks at the esophagojejunostomy occurred slightly more frequently (8.8%) than in the EGGCS (5.9%) and GGCS (7.2%); however, postoperative morbidity (36.1%) and early postoperative mortality (5.3%) were not increased compared to the multi-center quality assurance study results (EGGCS morbidity, 45%); EGGCS/GGCS mortality, 8%/8.9%). D2 lymphadenectomy was performed in 72.6% of cases (EGGCS: 70.9%). Multivariate analysis revealed splenectomy as an independent risk factor for postoperative morbidity and ASA status 3 or 4 as an independent risk factor for early postoperative mortality. The rate of splenectomies performed during gastric cancer surgery decreased substantially during the study period.Conclusions. Preoperative diagnostics were able to accurately predict resectability in almost 90% of patients which is substantially more than the corresponding results of both the EGGCS and the GGCS. In the future, more wide-spread use of EUS will play an increasing role as stage-dependent differentiation of therapeutic concepts gains acceptance. However, diagnostic accuracy of EUS needs to be improved. Our early postoperative outcome data demonstrate that the quality standard of gastric cancer care established by the EGGCS is being fulfilled at our institution in spite of distinct characteristics placing our patients at higher surgical risk. Besides being a valuable instrument of internal quality control, our study provides a good base for comparison with ongoing analyses on future developments in gastric cancer therapy.
Previously we have shown that hypoxia strongly induces the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 and -4 (PFKFB-3 and PFKFB-4) genes in several cancer cell lines via a HIF-dependent mechanism. In this paper we studied the expression and hypoxic regulation of PFKFB-4 and PFKFB-3 mRNA as well as its correlation with HIF-1α, HIF-2α, VEGF and Glut1 mRNA expression in the pancreatic cancer cell line Panc1 and two gastric cancer cell lines MKN45 and NUGC3. This study clearly demonstrated that PFKFB-3 and PFKFB-4 mRNA are expresses in MKN45, NUGC3 and Panc1 cancers cells and that both genes are responsive to hypoxia in vitro. However, their basal level of expression and hypoxia responsiveness vary in the different cells studied. Particularly, PFKFB-3 mRNA is highly expressed in MKN45 and NUGC3 cancer cells, with the highest response to hypoxia in the NUGC3 cell line. The PFKFB-4 mRNA has a variable low basal level of expression in both gastric and pancreatic cancer cell lines. However, the highest hypoxia response of PFKFB-4 mRNA is found in the pancreatic cancer cell line Panc1. The basal level of PFKFB-4 protein expression is the highest in NUGC3 gastric cancer cell line and lowest in Panc1 cells, with the highest response to hypoxia in the pancreatic cancer cell line. Further studies showed that PFKFB-3 and PFKFB-4 gene expression was highly responsive to the hypoxia mimic dimethyloxalylglycine, a specific inhibitor of HIF-α hydroxylase enzymes, suggesting that the hypoxia responsiveness of PFKFB-3 and PFKFB-4 genes in these cell lines is regulated by the HIF transcription complex. The expression of VEGF and Glut1, which are known HIF-dependent genes, is also strongly induced under hypoxic conditions in gastric and pancreatic cancer cell lines. The levels of HIF-1α protein are increased in both gastric and pancreatic cancer cell lines under hypoxic conditions. However, the basal level of HIF-1α as well as HIF-2α mRNA expression and their hypoxia responsiveness are different in the MKN45 and NUGC3 cancer cells. Thus, the expression of HIF-1α mRNA is decreased in both gastric cancer cell lines treated by hypoxia or dimethyloxalylglycine, but HIF-2α mRNA expression is not changed significantly in NUGC3 and slightly increased in MKN45 cells. Expression of PFKFB-4 and PFKFB-3 was also studied in gastric cancers and corresponding nonmalignant tissue counterparts from the same patients on both the mRNA and protein levels. The expression of PFKFB-3 and PFKFB-4 mRNA as well as PFKFB-1 and PFKFB-2 mRNA was observed in normal human gastric tissue and was increased in malignant gastric tumors. The basal level of PFKFB-4 protein expression in gastric cancers was much higher as compared to the PFKFB-3 isoenzyme. In conclusion, this study provides evidence that PFKFB-4 and PFKFB-3 genes are also expressed in gastric and pancreatic cancer cells, they strongly respond to hypoxia via a HIF-1α dependent mechanism and, together with the expression of PFKFB-1 and PFKFB-2 genes, possibly have a significant role in the Warburg effect which is found in malignant cells.
Gastric cancer is a malignant neoplasm. It is one of the major causes of premature death due to cancer in the world. Carcinogenesis process can take up to 30 years, therefore, stomach cancer develops primarily over the age of 50. However, the disease can occur at any age. The etiology of this disease is very complex, for example, environmental factors, persistent infection with Helicobacter pylori and smoking may be mentioned. However, it is estimated that about 20% of cases have been associated with a family occurrence. Symptoms, that may indicate the ongoing process of cancer, are non–specific. Because of the non–specific symptoms, gastric cancer is usually diagnosed at an advanced stage, when the only effective treatment is the complete resection of the affected organ, and the percentage of the 5–year survival rate is poor. For this reason, researchers are constantly looking for new diagnostic methods, including tumor markers which can accelerate diagnosis. The determination of tumor markers level could be also useful in the evaluation of remissions, monitoring recurrences and metastases. Investigations also provide novel therapeutic targets related, for example, to the molecular type of tumor, which would reduce the invasiveness and improve the quality of patient's life. This article presents and characterizes previously known and useful tumor markers associated with gastric cancer.
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Rak żołądka jest powszechnie występującym nowotworem złośliwym. Stanowi jedną z głównych przyczyn przedwczesnego zgonu z powodu chorób nowotworowych na świecie. Proces kancerogenezy może trwać nawet 30 lat, dlatego rak żołądka rozwija się przede wszystkim po 50. roku życia, jednakże zachorowania zdarzają się w każdej grupie wiekowej. Etiologia tej choroby jest bardzo złożona, składają się na nią m.in. czynniki środowiskowe, przetrwałe zakażenie bakterią Helicobacter pylori oraz palenie tytoniu. Szacuje się, że około 20% zachorowań jest związanych z występowaniem rodzinnym. Objawy, które mogą świadczyć o toczącym się procesie nowotworowym są nieswoiste. Ze względu na mało specyficzne objawy, rak żołądka jest zazwyczaj rozpoznawany w zaawansowanym stadium, kiedy jedynym skutecznym sposobem leczenia jest całkowita resekcja zajętego narządu, a odsetek 5–letnich przeżyć jest niski. Z tego względu, badacze wciąż poszukują nowych metod diagnostycznych, w tym markerów nowotworowych, które przyśpieszyłyby proces rozpoznania choroby. Oznaczanie stężenia markerów nowotworowych może być także przydatne w ocenie remisji, monitorowaniu wznowy oraz przerzutów. Badane są też nowe cele terapeutyczne, związane np. z typem molekularnym nowotworu, które pozwoliłyby ograniczyć inwazyjne zabiegi i polepszyć komfort życia pacjenta. W niniejszym artykule przedstawiono i scharakteryzowano dotychczas poznane oraz użyteczne markery nowo– tworowe dla raka żołądka.
Introduction: Gastric cancer is one of the most common tumors in the world. The pathogenesis of this cancer is not fully known. Among the risk factors for the disease there are: Helicobacter pylori infection, diet, alcohol consumption and smoking. On the other hand, it is assumed that the pathogenesis of the development is related to interdependence between risk factors and patient's genetic susceptibility. One of the genes involved in carcinogenesis can be ABCB1, whose protein product, P–glycoprotein, plays a protective function by removing xenobiotics from the cell into the extracellular environment. Polymorphisms of this gene can alter the protein product, leading to the loss of protective function and the increased risk of diseases development. Polymorphism T–129C can influence the formation of mRNA and thus, lead to changes in the quantity/activity of P–glycoprotein. The aim of this study was to evaluate the polymorphism at position T–129C in promoter region of ABCB1 gene in the group of patients with gastric adenocarcinoma. Material and methods: The material for the study consisted of 19 samples of the tissue taken from patients with gastric adenocarcinoma and 68 samples of peripheral blood taken from healthy donors. Genotyping of the T–129C was performed by using restriction fragments polymorphism method. Results: No statistically significant differences between the group of patients with gastric cancer and the healthy individuals were found. Conclusions: The polymorphism on position T–129C in promoter region of ABCB1 gene did not affect the risk of the development of gastric cancer. The obtained results require confirmation by investigating a large cohort of patients.
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Wstęp: Rak żołądka jest jedną z najczęstszych chorób nowotworowych na świecie. Patogeneza tego nowotworu nie została w pełni poznana. Wśród czynników ryzyka rozwoju choroby wymienia się: zakażenie Helicobacter pylori, niewłaściwą dietę, spożywanie alkoholu czy palenie tytoniu. Z drugiej strony, zakłada się, iż patogeneza rozwoju tego raka jest związana ze współzależnością pomiędzy czynnikami ryzyka a predyspozycją genetyczną samego pacjenta. Jednym z genów zaangażowanych w proces kancerogenezy może być ABCB1, którego produkt białkowy – glikoproteina P, poprzez usuwanie ksenobiotyków z komórki do środowiska pozakomórkowego, spełnia funkcję ochronną. Polimorfizmy tego genu mogą zmieniać jego produkt białkowy prowadząc do utraty funkcji ochronnej i zwiększonego ryzyka rozwoju chorób. Polimorfizm w pozycji T–129C może wpływać na powstawanie mRNA, a tym samym prowadzić do zmiany ilości/aktywności glikoproteiny P. Celem pracy była ocena polimorfizmu w regionie promotorowym genu ABCB1 w pozycji T–129C u pacjentów z gruczolakorakiem żołądka. Materiał i metody: Materiał do badania stanowiło 19 skrawków tkankowych pobranych od pacjentów z gruczolakorakiem żołądka oraz 68 prób krwi obwodowej pobranych od zdrowych krwiodawców. Genotypowanie w pozycji T–129C przeprowadzono za pomocą techniki polimorfizmu długości fragmentów restrykcyjnych. Wyniki: Nie wykazano istotnych statystycznie różnic pomiędzy grupą pacjentów z rakiem żołądka a grupą osób zdrowych. Wnioski: Polimorfizm w pozycji T–129C regionu promotorowego genu ABCB1 nie ma związku z rozwojem raka żołądka. Uzyskane w pracy wyniki badań wymagają potwierdzenia na większej grupie pacjentów.
Introduction: In the present thesis the association between the variants of C421A polymorphism of ABCG2 gene and the risk of gastric cancer development were searched. The occurrence of polymorphic variant 421 C > A leads to the weakening of the activity of BCRP protein which is encoded by the ABCG2 gene. Due to the presence of BCRP protein in the gastrointestinal tract and its protective role the reduction of the amount of BCRP protein which is the result of the tested polymorphism may lead to the increased predisposition to cancer development. The main aim of this study was to compare the frequency of C421A polymorphism genotypes between the examined and the control groups. Material and methods: The material for the research consisted of DNA isolated from 19 scraps of the tumor tissue taken from patients with gastric cancer and 44 samples of peripheral blood collected from healthy individuals. DNA was extracted from the tested materials by microcolumn-method. Then the obtained samples of DNA were subjected to polymerase chain reaction (PCR) to amplify the ABCG2 gene fragment. To determine C421A polymorphism genotypes ABCG2 gene fragments amplified by PCR the were analyzed by RFLP method using an digestive enzyme MseI. Results: All the examined patients irrespectively of gender, age and clinical stage showed the presence of genotype C/C, which is homozygous wild for C421A polymorphism. All 44 persons from the control group also showed the presence of genotype C/C. Conclusions: No differences in the occurrence of C421A genotypes between the study group and the control group were found. In both the groups 100% of the results for the C/C genotype were obtained. Due to the presence of only one genotype (C/C) for the C421A polymorphism in all the patients no relationship between the occurrence of C421A genotypes and tumor stage, age and gender of the examined patients was evaluated. Although no correlation between the C421A polymorphism and the susceptibility to the development of gastric cancer was found the exclusion of the participation of BCRP protein in the pathogenesis of this disease is possible only after the increase of the number of analyses on larger groups of respondents.
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Wstęp: W niniejszej pracy poszukiwano związku między występowaniem wariantów dla polimorfizmu C421A w obrębie genu ABCG2, a zwiększonym ryzykiem rozwoju raka żołądka. Występowanie wariantu polimorficznego 421 C>A prowadzi do zmniejszonej aktywności białka BCRP, kodowanego przez gen ABCG2. Ze względu na obecność białka BCRP w obrębie przewodu pokarmowego i związaną z tym rolę ochronną, zmniejszenie ilości białka BCRP będące efektem badanego polimorfizmu może zwiększać predyspozycję do rozwoju raka. Głównym celem pracy było porównanie częstości występowania genotypów dla polimorfizmu C421A pomiędzy grupą badaną a kontrolną. Materiał i metody: Materiał do badań stanowiło DNA wyizolowane z 19 mrożonych skrawków tkankowych pobranych od pacjentów z rakiem żołądka i z 44 prób krwi obwodowej pobranych od osób zdrowych. Izolację DNA z badanych materiałów biologicznych przeprowadzono wykorzystując metodę kolumienkową. Następnie, uzyskane próby DNA poddawano reakcji łańcuchowej polimerazy, by powielić badany fragmentu genu ABCG2. Celem określenia genotypów dla polimorfizmu C421A na mnożony w reakcji PCR fragment genu ABCG2 poddawano analizie metodą RFLP z użyciem enzymu MseI. Wyniki: U wszystkich badanych, bez względu na płeć, wiek oraz stopień zaawansowania klinicznego raka żołądka, wykazano obecność genotypu C/C, czyli homozygoty dzikiej dla polimorfizmu C421A. Wśród 44 osób z grupy kontrolnej również u wszystkich stwierdzono genotyp C/C. Wnioski: Nie wykazano różnic w częstości występowania genotypów dla polimorfizmu C421A między grupą badaną i kontrolną. W obydwu grupach zaobserwowano tylko jeden z możliwych genotypów dla badanego polimorfizmu - genotyp C/C. Z uwagi na stwierdzenie u wszystkich badanych osób z obu grup tylko genotypu C/C dla polimorfizmu C421A nie oceniano zależności między występowaniem genotypów C421A a stopniem zaawansowania nowotworu, wiekiem i płcią badanych osób. Mimo, że nie wykazano korelacji między polimorfizmem C421A a podatnością na rozwój raka żołądka, jednoznaczne wykluczenie udziału białka BCRP w patogenezie tej jednostki chorobowej jest możliwe dopiero po przeprowadzeniu większej ilości analiz na większych grupach badanych.
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