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

Combined Tumor Cell-Based Vaccination and Interleukin-12 Gene Therapy Polarizes the Tumor Microenvironment in Mice

Tumor progression depends on tumor milieu, which influences neovasculature formation and immunosuppression. Combining immunotherapy with antiangiogenic/antivascular therapy might be an effective therapeutic approach. The aim of our study was to elaborate an anticancer therapeutic strategy based on the induction of immune response which leads to polarization of tumor milieu. To achieve this, we developed a tumor cell-based vaccine. CAMEL peptide was used as a B16-F10 cell death-inducing agent. The lysates were used as a vaccine to immunize mice bearing B16-F10 melanoma tumors. To further improve the therapeutic effect of the vaccine, we combined it with interleukin (IL)-12 gene therapy. IL-12, a cytokine with antiangiogenic properties, activates nonspecific and specific immune responses. We observed that combined therapy is significantly more effective (as compared with monotherapies) in inhibiting tumor growth. Furthermore, the tested combination polarizes the tumor microenvironment, which results in a switch from a proangiogenic/immunosuppressive to an antiangiogenic/immunostimulatory one. The switch manifests itself as a decreased number of tumor blood vessels, increased levels of tumor-infiltrating CD4+, CD8+ and NK cells, as well as lower level of suppressor lymphocytes (Treg). Our results suggest that polarizing tumor milieu by such combined therapy does inhibit tumor growth and seems to be a promising therapeutic strategy

Fat Cats? : A Case for the Swedish Managers' Making Sense of the Developing Markets

In this thesis, I report a set of four studies designed to enhance the understanding of how managers of multinational enterprises (MNEs) perceive and make sense of their business environment under the conditions of gradual, long term environmental change. The focus lies on immanent sensemaking, a process occurring under the conditions of such an environmental change, which fails to give rise to a cosmology episode and consequently energise sensemaking as it has been traditionally understood. More specifically, the investigation is set on the evolution of Swedish MNE managers’ mental frames reflecting the growing importance of what is called developing markets. In the first study, I offer a qualitative probe into the mental frames held by five top managers of a selected MNE. The managers were interviewed and from these interviews, the managers’ mental frames were reconstructed. This study follows a design commonly used in sensemaking research. In the second study, I track the evolution of mental frames of top executives as expressed in CEOs’ letters to shareholders in a sample of 22 largest Swedish MNEs between 1991 and 2015. I juxtapose this with macroeconomic data reflecting the investigated environmental change. In the third study, I use the same data to investigate the intensity of sensemaking activities of the managers over the years. In the fourth study, I report results of a cluster analysis of the investigated companies. With the use of methods borrowed from psychological research, these four studies allow me to extend the sensemaking perspective to incorporate what is called immanent sensemaking, i.e. a sensemaking activity of low intensity and low cognitive strain, which allows for modification of extant mental frames in the face of slowly paced environmental changes which are unlikely to energise what is called episodic sensemaking, i.e. intensive, strenuous cognitive activity. I also offer an early attempt at conducting a sensemaking investigation of data of quantitative character

Fat Cats? : A Case for the Swedish Managers' Making Sense of the Developing Markets

In this thesis, I report a set of four studies designed to enhance the understanding of how managers of multinational enterprises (MNEs) perceive and make sense of their business environment under the conditions of gradual, long term environmental change. The focus lies on immanent sensemaking, a process occurring under the conditions of such an environmental change, which fails to give rise to a cosmology episode and consequently energise sensemaking as it has been traditionally understood. More specifically, the investigation is set on the evolution of Swedish MNE managers’ mental frames reflecting the growing importance of what is called developing markets. In the first study, I offer a qualitative probe into the mental frames held by five top managers of a selected MNE. The managers were interviewed and from these interviews, the managers’ mental frames were reconstructed. This study follows a design commonly used in sensemaking research. In the second study, I track the evolution of mental frames of top executives as expressed in CEOs’ letters to shareholders in a sample of 22 largest Swedish MNEs between 1991 and 2015. I juxtapose this with macroeconomic data reflecting the investigated environmental change. In the third study, I use the same data to investigate the intensity of sensemaking activities of the managers over the years. In the fourth study, I report results of a cluster analysis of the investigated companies. With the use of methods borrowed from psychological research, these four studies allow me to extend the sensemaking perspective to incorporate what is called immanent sensemaking, i.e. a sensemaking activity of low intensity and low cognitive strain, which allows for modification of extant mental frames in the face of slowly paced environmental changes which are unlikely to energise what is called episodic sensemaking, i.e. intensive, strenuous cognitive activity. I also offer an early attempt at conducting a sensemaking investigation of data of quantitative character

Sposób ochrony powierzchni ziemi przed skutkami podziemnych robót górniczych opis patentowy nr 37682 /

Tyt. z ekranu tyt.Udzielono 6 marca 1954 r.Opublikowano 30 lipca 1955 r.Dostępny także w wersji drukowanej.Tryb dostępu: Internet

Sposób magnetycznego wzbogacania rud żelaznych oraz innych minerałów, zawierających żelazo opis patentowy nr 33336 /

Tyt. z ekranu tyt.Zgłoszono 18 lipca 1946 r.Udzielono 13 sierpnia 1947 r.Opublikowano 10 kwietnia 1948 r.Dostępny także w wersji drukowanej.Tryb dostępu: Internet

The crime of forcing explanations by public officials during the hearing

Tytuł mojej pracy to wymuszanie wyjaśnień przez funkcjonariuszy publicznych podczas przesłuchania. Celem niniejszej pracy jest przedstawienie ogólnej problematyki wyżej wymienionego przestępstwa oraz skupienie się na metodach stosowanych przez polską policję podczas przesłuchania. Rozdział pierwszy został poświęcony wyjaśnieniu pojęcia przesłuchania oraz dotyczy zakazów uregulowanych w polskiej procedurze karnej dotyczących przebiegu przesłuchania. W powyższym rozdziale warta omówienia również jest problematyka niedopuszczalności przeprowadzenia oraz wykorzystania dowodu z art 168a kodeksu postępowania karnego. Następnie zostały omówione podstawowe pojęcia, które zostały użyte przez ustawodawcę w art 246 kodeksu karnego, regulującym odpowiedzialność za stosowanie przemocy podczas przesłuchania. Rozdział 3 został poświęcony porównaniu art 246 kodeksu karnego do podstawowych zasad zawartych w konstytucji oraz EKPcz. Następnie zostały opisane metody fizycznego oraz psychicznego znęcania się stosowane podczas przesłuchania. Zostało również wspomniane, jakimi pobudkami kierują się funkcjonariusze publiczni podczas przesłuchania stosując przemoc. W rozdziale 5 zostało omówione prawo do obrony oraz problematyka fałszywego przyznania się do winy. Przykładowo zostały wskazane techniki, które mogą powodować fałszywe przyznanie się do popełnienia przestępstwa oraz rodzaje fałszywego przyznania się. W kolejnym rozdziale zostało poddane analizie orzecznictwo polskich sądów, zostały przedstawione metody stosowane w konkretnych sprawach oraz wysokość kary wymierzonej za popełnienie powyższego przestępstwa. W rozdziale 7 zostały opisane przypadki znęcania się przez funkcjonariuszy publicznych podczas przesłuchania. Najpierw opisano przypadki mające miejsce w Polsce, a następnie w innych krajach takich jak: Rosja, Syria czy Anglia. Na sam koniec zostały przedstawione statystyki policyjne dotyczące przedmiotowego przestępstwa, które miały na celu ukazanie jak na przestrzeni piętnastu lat zmieniała się liczba wszczętych postępowań w stosunku do przestępstw stwierdzonych. Zakończenie zawiera wnioski dotyczące prawnej ochrony osób przesłuchiwanych, stosunku wymiaru sprawiedliwości do przestępstwa wymuszania wyjaśnień oraz zróżnicowania metod stosowanych celem wymuszania przyznania się do winy.The title of my thesis is the explanation extortion by public officials during the hearing. The aim of this study is to present the general problems of the above-mentioned crimes and focus on methods used by Polish police during interrogation. It presents the problem of evidence in a criminal trial and they are explained the terms used in Article 246 of the Criminal Code. It also presents the basic principles contained in the Constitution to protect the persons interviewed. This paper presents the methods used by public officials to force an explanation. Were also analyzed Polish jurisdictions and cases that presented enforcement explanations in Poland and in other countries. At the end they were presented police statistics showing the ratio of initiated proceedings to the offenses detected

How to Handle an Internal Venture? : The Effect of Relatedness on the Outcomes of Corporate Venturing

This paper uses event history analysis to investigate the effects of relatedness on three different outcomes of corporate venturing, identified as retention, termination, and spin-off. For this purpose, relatedness is defined as the degree to which the venture’s activity matches or overlaps with the parent’s activity. Drawing from literature on relational fit, we argue that highly related ventures would be retained, moderately related ones spun off, and unrelated ones would be probable candidates for termination. However, highly related ventures may be likely to pose internal threat to the parent, and consequently be candidates for termination for political reasons as well. This raises the average level of relatedness of terminated ventures above the average of spin-offs. The empirical findings derived from a sample consisting of 78 ventures launched and developed by a number of companies across the Swedish economy give support to our expectations. The highly related ventures were found to be either terminated or retained, moderately related ones were likely to be spun off, and unrelated ones typically faced termination. This supports our hypothesis that relatedness has an impact on how the internal venture is dealt with. We follow with implications for the practice of corporate venturing management

How to Handle an Internal Venture? : The Effect of Relatedness on the Outcomes of Corporate Venturing

This paper uses event history analysis to investigate the effects of relatedness on three different outcomes of corporate venturing, identified as retention, termination, and spin-off. For this purpose, relatedness is defined as the degree to which the venture’s activity matches or overlaps with the parent’s activity. Drawing from literature on relational fit, we argue that highly related ventures would be retained, moderately related ones spun off, and unrelated ones would be probable candidates for termination. However, highly related ventures may be likely to pose internal threat to the parent, and consequently be candidates for termination for political reasons as well. This raises the average level of relatedness of terminated ventures above the average of spin-offs. The empirical findings derived from a sample consisting of 78 ventures launched and developed by a number of companies across the Swedish economy give support to our expectations. The highly related ventures were found to be either terminated or retained, moderately related ones were likely to be spun off, and unrelated ones typically faced termination. This supports our hypothesis that relatedness has an impact on how the internal venture is dealt with. We follow with implications for the practice of corporate venturing management