Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

Osteopontin (OPN) is a pleiotropic protein, important in bone remodeling and immune system signaling. OPN is synthesized in a variety of cells and tissues. It can be found not only in bone cells but also in immune cells (B and T lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, macrophages, neutrophils, and dendritic cells). OPN regulates T-helper 1/T-helper 2 (Th1/Th2) balance, stimulates B cells to antibodies production, regulates macrophages and neutrophils function, and activates dendritic cells. A number of factors, including hormones, cytokines, and polymorphisms of promoter region of OPN gene, regulate protein expression. OPN and variants of the OPN gene have been associated with the pathogenesis of multiple disorders, including systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, systemic sclerosis, inflammatory bowel diseases, asthma, type 1 diabetes, and many other. However, some studies gave different or inconclusive results. Thus, the role of OPN polymorphic variants in autoimmune diseases needs to be better defined and explored as a diagnostic and therapeutic target to monitor and treat immune-mediated conditions

“Hand-foot” syndrome – after liposomal pegylated doxorubicin in patients with the ovarian cancer recurrence (own experiences)

Abstract Aim: To present our own experience with pegylated liposomal doxorubicin applied in ovarian cancer patients. Material and methods: The group of 32 patients with ovarian cancer was treated with pegylated liposomal doxorubicin (LPD) in Klinika Onkologii Klinicznej Centrum Onkologii Branch Gliwice between the years 2004 and 2007. Median age was 47 years. The histoclinical variables potentially influencing the occurrence of the hand-foot syndrome were analyzed. Results: Hand-foot syndrome has been observed in 11 patients (34,4%) treated with the LPD. The lesions have been present on the skin of hands, feet, elbow and knee joints and armpits. In the analyzed group of patients, the risk of the hand-foot syndrome occurrence increased, however non-significantly, with the increase of number of cycles including LPD (p=0,069) and the number of previous lines of chemotherapy (p=0,067). Other analyzed factors had no negative influence on the hand-foot syndrome occurrence. Conclusions: It is important to inform the patients about the risk of the hand-foot syndrome occurrence and its management. Early diagnosis allows to prevent the worsening of the hand-foot syndrome and makes it possible to continue the chemotherapy without the necessity of dose reduction and breaking from the therapy

Bevacizumab in the 1st line treatment of triple negative metastatic breast cancer patient — case report and review of the literature

Wprowadzenie. Angiogeneza i nadekspresja VEGF (Vascular Endothelial Growth Factor) odgrywają istotną rolę w rozwoju wielu typów nowotworów. Rola bewacyzumabu, humanizowanego przeciwciała anty-VEGF, w leczeniu chorych na rozsianego raka piersi pozostaje niejednoznaczna. Celem pracy jest przedstawienie przypadku chorej na potrójnie ujemnego, rozsianego raka piersi, która odniosła długotrwalą korzyść z immunochemioterapii jako pierwszej linii leczenia. Opis przypadku. U 57-letniej chorej na raka przewodowego piersi prawej, po szerokim wycięciu guza i limfadenektomii pachowej prawostronnej (pT1N0M0) oraz uzupełniającej chemio- i radioterapii, po czterech latach od zakończenia leczenia rozpoznano rozsiew choroby do płuca lewego (dwie zmiany) i węzłów chłonnych śródpiersia. Chora została zakwalifikowana do immunochemioterapii — paklitaksel z bewacyzumabem. W wyniku leczenia uzyskano znamienne zmniejszenie wymiarów zmian przerzutowych. Nie obserwowano poważnych działań niepożądanych terapii, po zakończeniu leczenia paklitakselem kontynuowano podawanie bewacyzumabu w ramach leczenia podtrzymującego. Od października 2009 r. do września 2013 r. chora otrzymała 70 wlewów bewacyzumabu. We wrześniu 2013 r. leczenie zakończono z uwagi na progresję wielkości zmian w płucu lewym, nowych zmian przerzutowych nie obserwowano. Chora została zakwalifikowana do stereotaktycznej radioterapii.Dyskusja. Jak dotąd skuteczność bewacyzumabu w leczeniu pierwszej linii u chorych na rozsianego raka piersi oceniono w trzech randomizowanych badaniach III fazy. We wszystkich tych badaniach stwierdzono znamienne wydłużenie PFS, bez istotnego zysku w zakresie OS. Na podstawie danych z literatury można przypuszczać, że konieczne jest wyodrębnienie podgrupy chorych, które odniosą największą korzyść z leczenia antyangiogennego. Aktualne doniesienia sugerują, ze najpewniej są to chore na potrójnie ujemnego raka piersi, które otrzymują bewacyzumab w skojarzeniu z chemioterapią w pierwszej linii leczenia, podobnie jak opisana przez nas chora.Introduction. Angiogenesis and VEGF (vascular endothelial growth factor) over expression play an important role inthe growth and development of many kinds of cancers. The role of bevacizumab, humanised, anti-VEGF antibody, intreatment of patients with metastatic breast canser (MBC) is still an open question. The aim of this paper is to present a case report of the use of bevacizumab with chemotherapy in the first line treatment of triple negative MBC.Case. We present the case of a 57-year-old woman with infiltrating ductal carcinoma of the right breast (pT1N0M0, TNBC). She underwent wide excision of the tumour with the excision of right axillary lymph nodes, adjuvant chemoterapy and radiotherapy. Four years later metastases in the left lung (two lesions) and mediastinum occured. For this reason the patient started immunochemotherapy — paclitaxel and bevacizumab. She ended paclitaxel after nine cycles, and continued bevacizumab as a maintenance. We observed a marked decrease in size of the metatstatic lesions. No serious adverse events during treatment were noted. From October 2009 to September 2013 the patient received 70 doses of bevacizumab. In September 2013 the treatment was ended due to progression of the size of the lung metastases. No new site of metastases was noted. The patient was considered suitable for stereotactic radiosurgery.Discussion. To date three randomised, multicenter studies, which evaluated effectiveness of adding bevacizumab to chemotherapy were performed. In all trials significant prolongation of progression-free survival (PFS) was observed but with no statistically significant influence on overall survival (OS). The toxicity of the combined treatment was higher. Many experts put a great emphasis on the need to discover a group of patients who will gain a significant benefit from antiangiogenic treatment. Reports in the literature indicate that probably the greatest benefit from adding bevacizumab to the chemotherapy is gained by women with triple-negative breast cancer, who receive bevacizumab as first-line treatment after cancer progression, as our patient described above

Dietary sodium sources in hypertensive patients

Background: Reducing dietary salt intake is the method recommended by the experts as the non-pharmacological treatment of hypertension. The purpose of this study was to evaluate the amount of dietary sodium intake by hypertensive patients and to analyze the factors affecting sodium intake. The frequency of consumption of dietary products with high sodium content was also analyzed. Material and methods: We recruited for the study 60 patients with uncomplicated chronic hypertension, between 40 and 80 years old. A proprietary questionnaire was used during the study. The first part of the questionnaire included questions about gender, age, body weight, body height. The second part was a questionnaire on the frequency of consumption of sodium-rich products. It included 6 food groups. Another component of the study was a 24-hour dietary recall collected from two working days and one holiday. Analysis of the patient's diet was carried out using ALIANT software. The database was created in Microsoft Excel and statistical analyses were performed using SPSS version 28. Results: In the study group, all respondents exceeded the salt intake standards recommended by scientific societies. The amount of sodium intake among men was significantly higher than in women (p = 0.011). There was no correlation between age, body mass index, place of residence or education and daily sodium intake. Among sodium-containing foods, patients most frequently consumed pizza, with 76.67% of respondents consuming it once a month or more often. The most commonly used condiment was table salt, used by 95% of respondents. Conclusions: Patients suffering from uncomplicated hypertension do not achieve the target of dietary sodium restriction to the values recommended in scientific guidelines. As dietary sodium intake standards are exceeded, hence the need for more intensive nutrition education among hypertensive patients

Mnogie nowotwory pierwotne u kobiet nosicielek mutacji genu BRCA1 – dwa przypadki kliniczne

Mutations of BRCA1 and BRCA2 genes account for the majority of hereditary breast and ovarian cancers. So far, risk-reducing salpingo-oophorectomy has been the most effective strategy for gynecological cancer prevention in susceptibility gene mutation carriers. It does not prevent, however, from the occurrence of primary peritoneal cancer. We present two clinical cases of patients with the BRCA1 gene mutation. Both patients had a family history of cancer and both were presenting with metachronic malignances. The first patient, whose mother suffered from breast and ovarian cancer, was diagnosed with left breast cancer in 2004. The patient was 44 years old at diagnosis. Genetic testing revealed the BRCA1 gene mutation. A breast conserving therapy (BCT) was conducted, followed by chemotherapy, radiotherapy and immunotherapy with trastuzumab due to HER2 overexpression. Due to BRCA1 mutation, in November 2005, prophylactic hysterectomy with appendages was performed. Histological examination revealed bilateral ovarian cancer (adenocarcinoma G3) with metastasis to the paraaortal lymph node. The patient received six cycles of chemotherapy: paclitaxel and carboplatin. Ovarian cancer relapsed 3 years later. After that the patient received 5 lines of chemotherapy and finally died due to disease progression in September 2011. The second patient, a 49-year-old woman, was diagnosed with breast cancer in July 2003 and subsequently treated with neoadjuvant chemotherapy, breast conserving surgery and radiotherapy. Genetic testing was also performed and revealed the BRCA1 gene mutation. A year earlier the patient had undergone hysterectomy with appendages due to uterine myomas. Three of her five sisters suffered from breast and ovarian cancer. The patient’s father died of colorectal cancer. The patient remained under surveillance. Because of the increasing level of Ca-125 (since October 2004), PET-CT was performed and revealed a tumor lesion of the peritoneum. Histological examination from the biopsy confirmed primary peritoneal cancer (papillary serous adenocarcinoma – primary peritoneal carcinoma). Reexamination of the tissues from hysterectomy with appendages was also performed and revealed an adenocarcinoma in the right ovary. Pathologic examination excluded metastasis of a breast cancer. Pathomorphology of the ovarian lesion was also different than in the lesions of the peritoneum. Thus, three different tumor types (breast, ovarian and peritoneal cancer) coexisted independently. The patient received chemotherapy: paclitaxel and cisplatin. Later on, due to disease progression she was treated with five consecutive chemotherapy regimens and hormonal therapy. The patient died in January 2008. These case illustrate that genetic diagnosis may be critical for the overall treatment plan.Za większość przypadków dziedzicznego raka piersi i jajnika odpowiadają mutacje genów BRCA. Obecnie najskuteczniejszą metodą prewencji raka jajnika jest obustronne usunięcie przydatków, niegwarantujące jednak zahamowania rozwoju pierwotnego raka otrzewnej. Przedstawiono przypadki dwóch chorych, z dodatnim wywiadem rodzinnym, mutacją genu BRCA1, u których stwierdzono nowotwory metachroniczne. U pierwszej chorej, której matka chorowała na nowotwór piersi i jajnika, w 2004 r. rozpoznano raka piersi lewej. Zastosowano operację oszczędzającą, uzupełniającą chemioterapię, radioterapię oraz immunoterapię trastuzumabem z uwagi na nadekspresję HER2. Ze względu na mutację genu BRCA1 u chorej wykonano operację profilaktycznego usunięcia macicy z przydatkami. Badanie histopatologiczne wykazało ognisko gruczolakoraka w obu jajnikach oraz w węźle chłonnym paraaortalnym. Zastosowano VI cykli chemioterapii: paklitaksel i karboplatyna. Nawrót raka jajnika stwierdzono trzy lata później. Chora otrzymała kolejnych V linii chemioterapii i zmarła w sierpniu 2011 r. z powodu progresji choroby. Druga chora, 49-letnia, leczona od lipca 2003 r. z powodu raka piersi prawej – neoadjuwantowa chemioterapia, BCT, radioterapia. U chorej stwierdzono mutację genu BRCA1. Rok wcześniej usunięto macicę z przydatkami z powodu mięśniaków. Trzy z pięciu sióstr kobiety chorowały na raka piersi i jajnika. Ojciec chorej zmarł z powodu raka jelita grubego. Chora pozostawała pod ścisłą kontrolą. Z powodu narastającego stężenia markera Ca-125 (od października 2004 r.) wykonano PET-TK, stwierdzając nowotworowe zajęcie otrzewnej. Badanie histopatologiczne materiału biopsyjnego wykazało gruczolakoraka otrzewnej, a ponowna ocena materiału z operacji usunięcia macicy z przydatkami, ognisko gruczolakoraka w jajniku prawym. Histopatolog wykluczył przerzut raka piersi i jednoznacznie określił odmienność morfologii zmian w otrzewnej od zmiany w jajniku. U chorej rozpoznano trzy niezależne nowotwory. Zastosowano chemioterapię: cisplatyna i paklitaksel. Następnie, z powodu progresji choroby, zastosowano V kolejnych linii chemioterapii oraz hormonoterapię. Chora zmarła w styczniu 2008 r

Stężenie interleukiny 2 i interleukiny 10 u pacjentów z cukrzycą typu 2 i rakiem okrężnicy

Introduction. The risk of colon cancer (CC) develop­ment is increased significantly among patients with type 2 diabetes (T2DM). A mechanism responsible for a higher prevalence of CC among diabetic patients may be associated with disturbances of the immune system. Cytokines — interleukin-2 (IL-2) and interleukin-10 (IL- -10) play relevant role in the immune response. The aim of this study was to investigate the differences in the immunological state in terms of IL-2 and IL-10 levels among groups of patients with T2DM, patients with CC, patients with T2DM and CC and patients without these diseases. Material and methods. 80 patients were included in the tests and split into 4 groups: group 1 — 24 patients with T2DM, group 2 — 24 patients with CC, group 3 — 10 patients with CC and T2DM, and group 4 — 22 persons without T2DM or CC. Colonoscopy was per­formed for all the patients. All cases of colon cancer were confirmed by histopathological examination. Laboratory measurements included blood tests such as fasting glucose, insulin, C-peptide and HbA1c. The serum concentration of IL-2 and IL-10 was determined by the immunoenzymatic (ELISA) method. Results. The concentration of IL-2 was statistically higher in the group of patients with T2DM and CC than in the groups of patients without those diseases (4.21 ± 1.61 SE pg/ml vs. group 1 — 1.57 ± 0.44 SE pg/ml, group 2 — 1.64 ± 0.27 SE pg/ml, group 4 — 1.95 ± 0.47 SE pg/ml; p &lt; 0.05). There were no statistically significant differences in the concentrations of IL-10 in patients with T2DM and CC compared with other subjects. The level of fasting glucose and HbA1c in the groups of patients with T2DM (group 1) and T2DM with CC (group 3) was statistically higher than in the groups of patients without T2DM. There were no statistically significant differences between the groups in levels of insulin, C-peptide and HOMA-IR. Conclusions. The concentration of IL-2 was statistically higher in the group of patients with T2DM and colon cancer than in other groups. Elevated level of IL-2 can be a marker of an increased risk of CC in people with type 2 diabetes. It might be useful in indicating a group of patients with differences in immune system particu­larly susceptible to the development of colon cancer.  Wstęp. U chorych na cukrzycę stwierdza się istotnie zwięk­szone ryzyko raka jelita grubego. Mogą być za to odpo­wiedzialne m.in. zaburzenia układu immunologicznego. Istotną rolę w odpowiedzi immunologicznej odgrywają cytokiny — interleukina 2 (IL-2) i interleukina 10 (IL-10). Celem pracy była ocena stężenia we krwi wybranych cy­tokin — IL-2 oraz IL-10 — u pacjentów z cukrzycą typu 2 i rakiem jelita grubego w porównaniu z osobami z cukrzy­cą typu 2 bez raka jelita grubego, z rakiem jelita grubego bez cukrzycy oraz bez obu tych patologii. Materiał i metody. Do badania włączono 80 chorych, których podzielono na 4 grupy — grupa 1 (24 osoby) z cukrzycą typu 2, grupa 2 (24 osoby) — z rakiem jelita grubego bez cukrzycy, grupa 3 (10 osób) —– z rakiem jelita grubego oraz cukrzycą typu 2, grupa 4 (22 oso­by) — grupa kontrolna bez cukrzycy oraz bez raka jelita grubego. Wszyscy pacjenci mieli wykonaną kolonoskopię. U osób z nowotworem jelita grubego potwierdzono rozpo­znanie w badaniu histopatologicznym. Przeprowadzono badania laboratoryjne obejmujące ocenę glikemii na czczo, stężenie insuliny i peptydu C oraz odsetek hemoglobiny glikowanej HbA1c. Stężenie IL-2 i IL-10 oznaczano metodą immunoenzymatyczną, stosując zestawy Human IL-2 ELISA KIT i Human IL-10 (DIACLONE Research, Francja). Wyniki. W grupie osób z cukrzycą typu 2 i rakiem jelita grubego stwierdzono statystycznie wyższe wartości stężenia interleukiny 2 (4,21 ± 1,61 SE pg/ml) w porów­naniu z innymi grupami pacjentów (grupa 1 — 1,57 ± 0,44 SE pg/ml, grupa 2 — 1,64 ± 0,27 SE pg/ml, grupa 4 — 1,95 ± 0,47 SE pg/ml; p < 0,05). Nie stwierdzono istotnej statystycznie różnicy pomiędzy badanymi grupami pod względem stężeń IL-10. Obserwowano statystycznie istotny wyższy poziom glikemii na czczo oraz hemoglobiny glikowanej w grupach z cukrzycą typu 2 oraz z cukrzycą typu 2 z towarzyszącym rakiem jelita grubego. Nie wykazano statystycznie istotnej różnicy pomiędzy grupami w poziomach insulinemii, peptydu C ani wskaźnika HOMA-IR. Wnioski. W grupie osób z cukrzycą typu 2 i rakiem jelita grubego stwierdzono statystycznie wyższe war­tości stężenia interleukiny 2 w porównaniu z innymi grupami. Podwyższone stężenie IL-2 w surowicy krwi może być wskaźnikiem zwiększonego ryzyka raka jelita grubego u osób z cukrzycą typu 2. Można zasugero­wać, że pacjenci z cukrzycą typu 2 oraz podwyższonym stężeniem IL-2 w surowicy krwi powinni być objęci szczególnym nadzorem onkologicznym

Usefulness of osteopontin (OPN) determinations in ovarian cancer patients who underwent first-line chemotherapy

Abstract Introduction: Currently CA 125 is a marker of choice for monitoring ovarian cancer. Nonetheless, scientists are still searching for new markers, which could provide additional information for the evaluation of treatment, especially in patients with normal CA 125 levels, despite the progression of the disease. According to the latest reports, OPN can be a potential new marker. Aim: Estimation of usefulness of OPN determinations in the monitoring of ovarian cancer patients. Material and Methods: The study included 54 ovarian cancer patients, undergoing chemotherapy. Markers were measured before, during and after treatment. The dynamics of the change of OPN levels was shown on line graphs, using Microsoft Excel programme. Statistical analysis was performed by Kaplan-Meier method and log-rank test. Results: 44% of patients from the study group were found to have low CA 125 levels. In these cases only the increase of OPN concentration indicated recurrence of the disease. In 43% of patients the high initial CA 125 and OPN levels decreased during chemotherapy and complete regression was stated in these patients. Nevertheless, in 13/17 patients a repeated increase of OPN concentration signalling the recurrence, earlier than CA 125 and clinical recurrence manifestation, was observed. In 13% of patients high initial levels of markers did not decrease during chemotherapy, which correlated with the progression of the disease. Our study showed that only the CA 125 levels had a significant influence (p=0.00063) on the disease-free survival time. Conclusions: Our data suggest a potential usefulness of the OPN determinations in estimating ovarian cancer recurrence. Nonetheless, there was no correlation between the initial OPN concentration and the disease-free survival time

Pharmacotherapy of heart failure A.D. 2023. Expert opinion of Working Group on Cardiovascular Pharmacotherapy, Polish Cardiac Society

Heart failure (HF) remains one of the most common causes of hospitalization and mortality among Polish patients. The position of the Section of Cardiovascular Pharmacotherapy presents the currently applicable options for pharmacological treatment of HF based on the latest European and American guidelines from 2021–2022 in relation to Polish healthcare conditions. Treatment of HF varies depending on its clinical presentation (acute/chronic) or left ventricular ejection fraction. Initial treatment of symptomatic patients with features of volume overload is based on diuretics, especially loop drugs. Treatment aimed at reducing mortality and hospitalization should include drugs blocking the renin-angiotensin-aldosterone system, preferably angiotensin receptor antagonist/neprilysin inhibitor, i.e. sacubitril/valsartan, selected beta-blockers (no class effect — options include bisoprolol, metoprolol succinate, or vasodilatory beta-blockers — carvedilol and nebivolol), mineralocorticoid receptor antagonist, and sodium-glucose cotransporter type 2 inhibitor (flozin), constituting the 4 pillars of pharmacotherapy. Their effectiveness has been confirmed in numerous prospective randomized trials. The current HF treatment strategy is based on the fastest possible implementation of all four mentioned classes of drugs due to their independent additive action. It is also important to individualize therapy according to comorbidities, blood pressure, resting heart rate, or the presence of arrhythmias. This article emphasizes the cardio- and nephroprotective role of flozins in HF therapy, regardless of ejection fraction value. We propose practical guidelines for the use of medicines, profile of adverse reactions, drug interactions, as well as pharmacoeconomic aspects. The principles of treatment with ivabradine, digoxin, vericiguat, iron supplementation, or antiplatelet and anticoagulant therapy are also discussed, along with recent novel drugs including omecamtiv mecarbil, tolvaptan, or coenzyme Q10 as well as progress in the prevention and treatment of hyperkalemia. Based on the latest recommendations, treatment regimens for different types of HF are discussed