Czy metformina pomaga pacjentkom z rakiem endometrium?

Objectives: Since metformin was reported to decrease overall cancer incidence and mortality and to have antiproliferative and antiinvasive properties, we investigated the impact of metformin intake on survival in endometrial cancer patients. Material and methods: Medical records and survival data of 126 patients with endometrial cancer were analyzed retrospectively. U Mann-Whitney and chi-square tests were applied to compare clinicopathological features. Kaplan Meier model with log-rank test was used to compare survival in the subgroups. Cox proportional hazard model was applied to analyze the relationships between particular factors and overall survival. Results: 107 patients met study criteria and were divided into three groups: 1) patients with type 2 diabetes and metformin users (n=30), 2) patients with type 2 diabetes and metformin non-users (n=38), 3) patients without diabetes mellitus (n=39). No difference in survival between metformin users versus metformin non-users (p=0,86) was observed. Metformin intake, diabetes mellitus co morbidity, plasma glucose level and BMI appeared without influence on survival. When the analysis was restricted to the subgroup of type I endometrial cancer or to endometroid histological type, still neither metformin intake nor diabetes influenced the prognosis. Conclusions: Metformin intake does not alter overall survival in endometrial cancer patients. Diabetes mellitus has no influence on survival in endometrial cancer patients.Cel pracy: Wobec doniesień o korzystnym działaniu metforminy polegającym na zmniejszaniu zapadalności i umieralności na choroby nowotworowe oraz o jej właściwościach antyproliferacyjnych i hamujących naciekanie, w tej pracy postanowiliśmy zbadać wpływ metforminy na przeżycie pacjentek z rakiem endometrium. Materiał i metody: Retrospektywnej analizie poddane zostały historie chorób 126 pacjentek z rakiem endometrium. Cechy histopatologiczne porównano przy użyciu testów U Mann-Whitney i chi-kwadrat, a przeżycie pacjentek w podgrupach za pomocą estymatora Kaplana Meiera (test log-rank). Model Coxa zastosowano, żeby określić zależności pomiędzy poszczególnymi czynnikami a całkowitym czasem przeżycia. Wyniki: Do badania zakwalifikowano 107 pacjentek, które podzielono na 3 grupy: 1) pacjentki z cukrzycą typu 2 stosujące metforminę (n=30), 2) pacjentki z cukrzycą typu 2 nieleczone metforminą (n=38), 3) pacjentki niechorujące na cukrzycę typu 2. Nie zaobserwowano istotnej statystycznie różnicy w czasie całkowitego przeżycia pomiędzy pacjentkami leczonymi a nieleczonymi metforminą (p=0,86). Podobnie stosowanie metforminy, współistnienie cukrzycy typu 2, poziom glukozy we krwi i indeks masy ciała (BMI) nie miały wpływu na przeżycie chorych. Zawężając analizowaną grupę do raka endometrium typu I lub do histologicznego typu endometrioidalnego uzyskano takie same wyniki. Wnioski: Zażywanie metforminy nie ma wpływu na czas całkowitego przeżycia pacjentek chorych na raka endometrium. Współistnienie cukrzycy również pozostaje bez wpływu na przeżycie w tej grupie pacjentek

Choriocarcinoma complicated with intra-abdominal and intrapleural hemorrhage in pregnancy – case report

BackgroundChoriocarcinoma is a rare neoplasm, exceptionally uncommon during an ongoing pregnancy. The disease often has a metastatic character, causing severe symptoms from various anatomic sites like the lungs, central nervous system, vagina, pelvis, or liver. Due to the condition’s rarity, evidence on how to treat the choriocarcinoma originating during pregnancy remains scarce.Case presentationHere, we present a case of a patient who developed choriocarcinoma before the 29th week of gestation. The neoplasm had a metastatic character, resulting in hemorrhage complicated by a hypovolemic shock. The patient underwent an emergency cesarean section and several surgeries to stop the massive hemorrhage. The treatment of the choriocarcinoma included chemotherapy with methotrexate followed by an EMA-CO regimen. The patient had a complete response to the therapy. The neonate suffered from complications related to prematurity.ConclusionMetastatic choriocarcinoma can be a diagnostic and therapeutic challenge during ongoing pregnancy. Treatment of the disease can be associated with severe complications, but a complete response to chemotherapy is possible with a favorable long-term prognosis

COX-2 expression pattern is related to ovarian cancer differentiation and prognosis, but is not consistent with new model of pathogenesis

Objective: Numerous studies suggest that cyclooxygenase-2 (COX-2) is overexpressed in cancer. Our objective was to investigate the relationship between COX-2 expression in ovarian carcinoma and clinicopathological factors. An emphasis was put on the association with the new pattern of tumorigenesis that divides tumors into type I – less aggressive, and type II – more aggressive one. The prognostic significance of COX-2 expression was evaluated. Methods: Ovarian cancer tissues were obtained from 65 patients in FIGO III stage (23 with type I and 42 with type II ovarian cancer). COX-2 expression was evaluated by immunohistochemistry. The statistical analysis was performed in order to assess the connection between COX-2 expression and characteristic factors of ovarian cancer patients as well as the new division for type I and type II ovarian cancer. Results: COX-2 expression was detected in 91% of tissue samples. It was markedly elevated in well differentiated tumors (p=0.0041). The platinum - resistant tumors had significantly higher expression of COX-2 (p=0.0337). There was no difference between COX-2 expression in type I and type II ovarian cancer (p=0.6720). The COX-2 staining was not associated to age, CA125 level, the presence of ascites or any special histological type. An increased expression of COX-2 was an unfavorable prognostic factor for overall survival (p=0.0369) and progression-free survival (p=0.0218). Multivariate analysis confirmed that COX-2 overexpression is an independent unfavorable prognostic factor of shorter progression-free survival (p=0.048). Conclusions: COX-2 expression is an unfavorable prognostic factor for progression-free survival and overall survival in ovarian cancer. There is no relationship between COX-2 expression in ovarian cancer tissue and the examined model of ovarian cancer pathogenesis

Autoimmune response in lung cancer patients with neurological paraneoplastic syndromes

Aim of the study. The aim of this study was to evaluate granzyme B, perforin and FasL expression in peripheral blood mononuclear cells (PBMCs) in lung cancer patients and in paraneoplastic neurological syndromes (PNS). Clinical rationale for the study. Cellular immune response is activated as part of anti-tumour reaction of the malignancy-bearing host. Paraneoplastic neurological syndromes (PNS) are defined as indirect effects of cancer on the nervous system and are considered immune-mediated. Such stimulation of the immune system may limit the aggressiveness of cancer and the development of metastasis, and thereby improve survival. Granzyme B and perforin pathway, and Fas ligand (FasL) – Fas receptor interaction play an important role in cytotoxic response. Materials and Methods. Fifty-two patients were included in the study: 28 subjects with PNS and 24 subjects with lung cancer. PNS cases were diagnosed according to the Graus criteria. The presence of onconeural antibodies (anti-Hu/anti-Ri/anti-Yo/anti-Ma/Ta/anti-CV2/anti-amphiphysin/anti-myelin/anti-neuroendothelium/anti-MAG/anti-GAD) was detected with indirect immunofluorescence and confirmed with Line Blotting. The expression of granzyme B, perforin and FasL was detected in PBMCs with ELISA. Results. PPBMC-FasL expression was increased in lung cancer compared to other patient groups. The granzyme to FasL ratio was significantly higher in lung cancer patients with peripheral than with central PNS involvement. In a multiple regression model, sex was an independent factor influencing PBMC expression of granzyme and perforin. Conclusions. FasL expression in PBMCs is up-regulated in lung cancer patients. The interplay between granzyme B and FasL may be involved in the development of PNS at the level of the peripheral and the central nervous systems in different manners. Gender is associated with PBMC expression of granzyme B and perforin in lung cancer patients. Clinical Implications. The novel findings that we report broaden the current knowledge on PNS pathomechanism, with aspects that have not been previously explored. Our findings provide a rationale for further exploration of the granzyme B/FasL pathway with regards to its potential diagnostic value. However, our study is preliminary and needs further research, especially in the context of the prognostic value of the proposed markers

Występowanie raka szyjki macicy po histerektomii nadszyjkowej – badanie wieloośrodkowe

Objectives: Cervix-sparing hysterectomy due to benign conditions remains controversial, especially when the presumed risk of cervical cancer in the retained cervical stump is concerned. On the other hand, supracervical hysterectomy is associated with shorter operative time, decreased blood loss and decreased intraoperative complications. Moreover, beneficial effects of retaining the cervix on the pelvic statics and female psychosexual functioning have been suggested, although not yet proven. The aim: The aim of the study was to determine the frequency and types of cervical cancers in the retained cervical stump after supracervical hysterectomy performed due to benign diseases of the uterine corpus in four academic settings. Material and methods: Retrospective review of medical records of 903 women who underwent treatment due to cervical carcinoma in four departments participating in the study: Centre 1- 2nd Department of Gynecology, Medical University, Lublin (years: 2001- 2011); Centre 2- Department of Gynecology and Gynecologic Oncology, Military Institute of Medicine, Warsaw (years: 2002-2012); Centre 3- Katedra i Kliniki Położnictwa, Chorób Kobiecych i Ginekologii Onkologicznej II Wydziału Lekarskiego WUM, Warsaw (years: 2008-2013) and Centre 4- Department of Gynecologic Oncology, Poznań University of Medical Sciences, (years: 2000-2012). The occurrence rate of cervical stump carcinoma was reported in relation to patient age, time elapsed between supracervical hysterectomy and diagnosis stump cancer, and histological type of cancer. Results: Only 3 cases of cervical stump carcinoma (0.33%) were identified among the 903 investigated women. In all these cases, cervical stump cancers were diagnosed several years after supracervical hysterectomy. In one case the only treatment was radiotherapy, in one case only trachelectomy was performed, whereas in one case surgery followed by radiotherapy was used. Conclusions: It should be remembered that subtotal hysterectomy carries a risk, albeit relatively low, of developing stump cancer. Therefore, patients should be informed that after such operation further cervical cancer screening is mandatory. Moreover, subtotal hysterectomy should not be offered in populations at risk of developing cancer of the uterine cervix.Cel pracy: Wykonywanie histerektomii oszczędzającej szyjkę macicy z przyczyn innych niż nowotwór złośliwy jest coraz częściej wykonywaną procedurą ze względów farmakoekonomicznych, jak również psychospołecznych. Z drugiej jednak strony należy się liczyć z potencjalną możliwością rozwoju raka szyjki macicy u tak leczonych pacjentek. Przeprowadzenie zabiegu amputacji nadszyjkowej trzonu macicy wiąże się ze skróceniem czasu trwania zabiegu, mniejszą utratą krwi, spadkiem liczby powikłań śród- i pooperacyjnych oraz z krótszym okresem hospitalizacji. Dyskutowany jest również potencjalnie korzystny wpływ pozostawienia szyjki macicy na zachowanie prawidłowej statyki narządów miednicy mniejszej jak również funkcje seksualne, przy czym w chwili obecnej brak jest badań jednoznacznie potwierdzających to ostatnie założenie. Cel pracy: Celem pracy była ocena częstości występowania raka szyjki macicy oraz określenie jego typu histopatologicznego w przypadku przeprowadzenia zabiegu nadszyjkowej amputacji trzonu macicy. Materiał i metody: W badaniu retrospektywnym wykorzystano dane medyczne uzyskane od 903 pacjentek leczonych z powodu raka szyjki macicy w czterech Klinikach Ginekologicznych biorących udział w projekcie: ośrodek 1 – II Klinika Ginekologii UM, Lublin (lata 2001–2011); ośrodek 2 – Klinika Ginekologii i Ginekologii Onkologicznej Wojskowego Instytutu Medycznego, Warszawa (lata 2002–2012); ośrodek 3 – Katedra i Kliniki Położnictwa, Chorób Kobiecych i Ginekologii Onkologicznej II Wydziału Lekarskiego WUM, Warszawa (lata 2008-2013) oraz ośrodek 4 – Klinika Onkologii Ginekologicznej UM, Poznań (lata 2000–2012). We wszystkich ośrodkach analizowano liczbę pacjentek leczonych z powodu raka szyjki macicy w zależności od obecności u pacjentki trzonu macicy w chwili przyjęcia, wieku pacjentki w chwili rozpoznania nowotworu, czasu jaki upłynął od amputacji trzonu oraz typu histopatologicznego nowotworu. Wnioski: Potencjalne ryzyko powstania raka w pozostawionym kikucie szyjki szacuje się na 1/1000 kobiet poddanych histerektomii subtotalnej. Przed przeprowadzeniem powyższego zabiegu należy w każdym przypadku dokładanie przeanalizować potencjalne czynniki rozwoju raka szyjki macicy. Pacjentki, u których przeprowadzono nadszyjkową amputację trzonu macicy, należy poinformować, że pomimo niewielkiego ryzyka wystąpienia raka szyjki macicy, muszą one kontynuować skrining cytologiczny

Modeling of Intracellular Taurine Levels Associated with Ovarian Cancer Reveals Activation of p53, ERK, mTOR and DNA-Damage-Sensing-Dependent Cell Protection

Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine’s suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine’s ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine’s cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transduction

Cavity ring-down spectroscopy of D2 ro-vibrational line with absolute frequency axis

International audienc

FROM AB INITIO CALCULATIONS TO SPECTRAL LINE SHAPE PARAMETRISATION FOR SPECTROSCOPIC DATABASES

International audienceHydrogen molecule in its ground electronic state perturbed by the helium atom constitutes the simplest system of molecule perturbed by atom. This gives possibility to make a link between the experiment and the theory from first principles. We utilize highly accurate cavity ring-down spectroscopy to study the H2-He collisions and interactions. In contrast to most of the previous studies, we directly superimpose theoretical profiles, originating from our ab initio calculations, on the experimental spectra without fitting any of the line-shape parameters. Within this approach not only the shapes of experimental lines are reliably reproduced, but also the underlying physics of molecular collisions can be traced. Besides the analysis of the basic line-shape effects (such as relaxation or phase changes of the internal states of the molecule), we also study the more sophisticated ones such as speed-dependent effects or velocity-changing collisions (complex Dicke narrowing parameter), which are particularly pronounced for the H2-He system. We achieved agreement at the 1% level between experimental data and ab initio calculations not reached before for any real system. In addition, we show that measured spectral line shapes can be interpolated within similar accuracy by Hartman-Tran line shape profile, which has been implemented as a standard for HITRAN database with β correction applied

CRDS measurements and ab initio calculations of collisional effects in pure D2

International audienceRecent progress in theoretical calculations of dissociation energies of H2, HD and D2 [1–2] gives predictions of the transition frequencies with uncertainty exceeding the level of 10-3 cm-1 for the first overtone band (2–0) [3]. Such predictions open a way for testing relativistic and quantum electrodynamics corrections. They give also the opportunity for searching for new physics like additional long-range hadron-hadron interactions [4]. At this level of accuracy the uncertainty of the H 2 (or its isotopologues) line position determination in Doppler limit becomes considerably affected by the line-shape effects [5] including asymmetry of the line shapes. Spectral line shapes of D2 transitions are atypical and difficult to model. First strategy for overcoming this problem is measuring the spectra at low pressures, where collisional effects are negligible [3]. However, it is experimentally challenging due to exceptionally low intensities of the quadrupole lines. Another approach is recording them at higher pressures and describe the collisions in a more sophisticated way. Here as an example of the second strategy, we present our preliminary results applied for very weak S(2) transition of deuterium in the 2-0 band, using ab initio calculations. Transition has been measured with the frequency-stabilized cavity ring-down spectroscopy (FS-CRDS) assisted by an optical-frequency comb [6,7], using experimental setup described in [8]. The line positions at high pressures, up to 1000 Torr, were measured with sub-MHz accuracy. Furthermore, to validate ab initio model, we extended our experiments to a wide range of temperatures. We compare it with ab initio quantum scattering calculations, where we obtain the generalized spectroscopic cross sections. The real and imaginary parts provide the speed-dependent collisional broadening γ(ν) and shifting δ(ν). The velocity-changing collisions, in turn, are described by hard-sphere approximation of the ab initio potential which is called the speed-dependent billiard-ball profile (SDBBP) [9]

Ultra accurate measurements and ab initio calculations of collisional effects in pure D2 .

International audienceWe present our experimental spectra of the very weak S(2) transition from the 2–0 band of molecular deuterium, measured with a frequency-stabilized cavity ring-down spectroscopy (FS–CRDS) assisted by the optical frequency comb (OFC). Experimental collisional broadening and shifting are compared with results of ab initio quantum scattering calculations