Social Behavior of Pet Dogs Is Associated with Peripheral OXTR Methylation

Oxytocin is a key modulator of emotional processing and social cognitive function. In line with this, polymorphisms of genes involved in oxytocin signaling, like the oxytocin receptor (OXTR) gene, are known to influence social behavior in various species. However, to date, no study has investigated environmental factors possibly influencing the epigenetic variation of the OXTR gene and its behavioral effects in dogs. Pet dogs form individualized and strong relationships with their owners who are central figures in the social environment of their dogs and therefore might influence the methylation levels of their OXTR gene. Here we set out to investigate whether DNA methylation within the OXTR promoter region of pet dogs is linked to their owner's interaction style and to the social behavior of the dogs. To be able to do so, we collected buccal epithelial cells and, in Study 1, we used pyrosequencing techniques to look for differentially methylated CpG sites in the canine OXTR promoter region on a heterogeneous sample of dogs and wolves of different ages and keeping conditions. Four identified sites (at positions -727, -751, -1371, and -1383 from transcription start site) showing more than 10% methylation variation were then, in Study 2, measured in triplicate in 217 pet Border Collies previously tested for reactions to an adverse social situation (i.e., approach by a threatening human) and with available data on their owners' interaction styles. We found that CpG methylation was significantly associated with the behavior of the dogs, in particular with the likelihood that dogs would hide behind their owner or remain passive when approached by a threatening human. On the other hand, CpG methylation was not related to the owners' behavior but to dog sex (at position -1371). Our findings underpin the complex relationship between epigenetics and behavior and highlight the importance of including epigenetic methods in the analysis of dog behavioral development. Further research is needed to investigate which environmental factors influence the epigenetic variation of the OXTR gene

Új immunterápias lehetősegek az emlőrák kezelésében

The prognostic value of tumor infiltrating lymphocytes in breast cancer has long been recognized by histopathologists. These observations were reaffirmed by recent immunohistochemistry and gene expression profiling studies that also revealed an association between greater chemotherapy sensitivity and extensive lymphocytic infiltration in early stage breast cancers treated with neoadjuvant chemotherapy. These results suggest that local anti-tumor immune response can at least partially control cancer growth and may mediate the antitumor effects of chemotherapy. However, until recently, there was no direct clinical evidence to demonstrate that enhancing anti-tumor immune response could lead to clinical benefit in breast cancer patients. The recent development of clinically effective immune checkpoint inhibitors made it possible to test the therapeutic impact of augmenting the local anti-tumor immune response. Two Phase I clinical trials using single agent anti-PD-1 (MK-3475, pembrolizumab) and anti-PD-L1 (MPDL3280A, atezolizumab) antibodies demonstrated close to 20% tumor response rates in heavily pretreated, metastatic, triple negative breast cancers. The most remarkable feature of the responses was their long duration. Several patients had disease control close to a year, or longer, which has not previously been seen with chemotherapy regimens in this patient population. A large number of clinical trials are currently underway with these and similar drugs in the neoadjuvant, adjuvant and metastatic settings to define the role of this new treatment modality in breast cancer

Klinikopatológiai szemléletű emlőrákkutatások

In the second half of the 20th century research focusing to breast carcinomas at the Semmelweis University had been mostly linked to the 2nd Department of Pathology. Nowadays, following the rapidly improving treatment modalities in breast cancer there is an increasing need for defining new predictive and prognostic markers. The modern molecular pathological approach helps tremendously in mapping the biological behavior of individual cases of breast cancers and meanwhile, it is one of the prerequisites of a more efficient treatment both in neoadjuvant and adjuvant settings, as well as in metastatic disease. We provide a brief review of the relevant results we have obtained in breast cancer research between 2000 and 2015

Clinicopathological Features and Prognosis of Pregnancy Associated Breast Cancer – A Matched Case Control Study

Pregnancy Associated Breast Cancer (PABC) manifests during pregnancy or within a year following delivery. We sought to investigate differences in management, outcome, clinical, histopathology and immunohistochemistry (IHC) characteristics of PABC and matched controls in a retrospective case control study. PABC and control patients were selected from breast cancer cases of women </=45 years, diagnosed in the 2nd Department of Pathology, Semmelweis University, Budapest, Hungary between 1998 and 2012. Histopathology information on tumor type, grade, size, T, N, lympho-vascular invasion (LVI), Nottingham Prognostic Index (NPI), associated in situ lesions and IHC charcteristics: ER, PgR, HER2, Ki67, p53 were recorded, IHC-based subtype was assessed, clinical, management and outcome data were analysed. Thirty-one breast cancer cases were pregnancy related. Clinical management data did not differ in cases and controls. Histopathology of disease at presentation was not significantly different, but NPI assessed the PABC group as having poor, whereas controls as having intermediate prognosis. Associated in situ lesion was more often high grade Extensive Intraductal Carcinoma Component (EIC) in PABC. Triple negative and LuminalB prol tumors predominated in PABC. Disease-free and overall survival was inferior compared to controls. PABC patients with LuminalB prol and Triple negative tumors had inferior outcomes. On multivariate analysis inferior prognosis of PABC was associated with pregnancy. Our study has demonstrated inferior outcome of PABC. Difference in tumor biology is reflected by the predominance of triple negative and LuminalB tumors in PABC. The strength of the study is the analysis of complete pathology and IHC data

Extracorporalis immunmoduláns kezelések alkalmazása akut gasztroenterológiai kórképekben = The use of extracorporal immunomodulatory treatments in acute gastroenterological disorders

Az akut, életet veszélyeztető gasztroenterológiai kórképek közül a súlyos akut pancreatitis és az akut májelégtelenség magas mortalitású kórképek, kezelésük napjainkban is kihívást jelent. Mindkét kórkép esetén jelentős sejtkárosodás jön létre, ezen felül a gyakran társuló infekció is túlzott immunválaszt, „citokinvihart” eredményezhet, amelynek kontrollálására a gyógyszeres próbálkozások nem jelentettek kellő hatékonyságú megoldást, ezért az extracorporalis technikák kerültek előtérbe. A citokin-adszorberek közül a CytoSorb alkalmazásával van jelenleg világszerte a legtöbb tapasztalat, amely kombinálható egyéb extracorporalis szervpótló kezelésekkel is. Két esetünk kapcsán szeretnénk bemutatni a jelenlegi terápiás lehetőségeinket, illetve tapasztalatainkat

Az FDG-PET-CT szerepe az emlőrák primer szisztémás kezelése során: a metabolikus változások és a patológiai remisszió összefüggései = The Role of FDG-PET-CT in the Evaluation of Primary Systemic Therapy in Breast Cancer: Links Between Metabolic and Pathological Remission

Introduction: FDG-PET-CT is highly sensitive in detection of viable tumour tissue, giving an importance for that in oncological diagnostics. Aim: The authors analysed retrospectively the relationship between metabolic response and changes in Ki-67, a proliferation marker. Methods: Staging FDG-PET-CT scans (before and after therapy) SUVs (Standardized Uptake Value), and morphological changes in the primary tumour and axillary lymph node region were evaluated in 30 patients with breast cancer. Calculated ΔSUV were compared with Ki-67 proliferation marker (measured in biopsies and surgical specimens). Results: The decrease of SUV and size were significant in the primary tumour and the axillary lymph node region. Decrease of Ki-67 was significant. Significant correlation was found between Ki-67 and SUV before therapy, initial Ki-67 and ΔSUV, and ΔKi-67 and ΔSUV. Conclusions: The metabolic changes were more sensitive in the measurement of the therapeutic response than morphological remission, and they correlated well with the pathological response, in not standardized clinical conditions even. Orv. Hetil., 2012, 153, 1958–1964. </jats:p

A várandósság alatti emlőrák kezelése = Treatment of pregnancy associated breast cancer

Terhességi emlőráknak a várandósság ideje alatt, illetve a szülést követő egy éven belül kialakuló rosszindulatú emlődaganatot nevezzük. Háromezer várandós nőből körülbelül 1-ben alakul ki. A tumor incidenciája növekedő tendenciát mutat, amelyben elsősorban a gyermekvállalás egyre későbbi életkorra való kitolódása játszhat szerepet. A várandós állapot késlekedést okozhat mind a diagnózis felállításában, mind a megfelelő kezelés elindításában. Közleményünkben egy 30 éves nőbeteg esetét ismertetjük, aki első terhességének 21. hetében önvizsgálat során észlelte a jobb emlő bőrének gyulladásos elváltozását, és a hónaljárokban levő megnagyobbodott nyirokcsomókat. Az antibiotikus kezelésre a páciens panaszai nem javultak, ezért az axillaris képlet vékonytű-aspirációs citológiai vizsgálatát végezték el, amelynek során metasztatikus emlőrák igazolódott. A klinikánkon végzett vizsgálat során cT4 cN3 lokoregionális kiterjedésű daganatot véleményeztünk. Az emlő bőrének elváltozása gyulladásos emlőrákra utalt, emellett axillaris, valamint supraclavicularis nyirokcsomó-konglomerátumot is tapintottunk. A core-bioptátum értékelése során hormonreceptor-negatív, Her-2-pozitív, grade III differenciáltságú invazív carcinoma igazolódott. Neonatológiai és onkológiai konzíliumot követően a beteg úgy döntött, hogy a várandósság alatt elzárkózik a kemoterápiás kezeléstől, ezért a 30. gesztációs héten elektív császármetszést végeztünk. A további vizsgálatok távoli áttétet nem igazoltak, így primer szisztémás kemoterápiát kezdtünk, majd ezt követően mastectomia és axillaris blokkdisszekció történt. Az eltávolított emlőállományban visszamaradt tumort a kórszövettani vizsgálat során már nem azonosítottunk, a szöveti kép alapján komplett patológiai remissziót véleményeztünk. A sugárkezelés befejezése után trastuzumabkezelést indítottunk. Az ellenőrző vizsgálatok a páciensnél eddig sem helyi kiújulást, sem távoli áttétet nem igazoltak. Az újszülött generalizált izomtónus-eloszlási zavarok miatt jelenleg is fejlődésneurológiai gondozás alatt áll. | Pregnancy-associated breast cancer (PABC) is defined as cancer of the breast diagnosed during pregnancy and up to 1 year postpartum. The crude incidence is 1/3000 pregnant women. As women delay childbearing the incidence of PABC increases with age. Young patients with PABC do not have worse prognosis compared with those with non-PABC; however, pregnancy can contribute to a delay in breast cancer diagnosis, evaluation, and treatment. Primary care physicians and gynecologists should be careful in the thorough workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment as early as possible following the established diagnosis. Authors report a case of a 30-year-old pregnant woman, who detected inflammatory signs of her right breast and a palpable axillary mass at the 21st week of gestation. Her symptoms did not improve with administration of antibiotics. Therefore fine needle aspiration biopsy of the axillary lump was performed, with the result of unequivocal diagnosis of metastatic invasive carcinoma. The patient was referred to the multidisciplinary tumor board of our Department at the 27st week of gestation with the symptoms of inflammatory breast cancer, palpable right axillary and supraclavicular lymph nodes. Core biopsy showed an ER and PR negative, Her-2 positive, grade 3, infiltrating ductal carcinoma of the breast. After multidisciplinary team consultation the patient declined any kind of therapy during her pregnancy. On the 30th week of gestation caesarean section was performed. The premature baby girl was treated in the Neonatal Intensive Care Unit. Imaging modalities revealed no evidence of distant metastases short after the delivery. After 6 cycles of chemotherapy (docetaxel-doxorubicin-cycclophosphamid) the patient underwent right mastectomy and axillary lymph node dissection. Complete pathological response was diagnosed, since no residual tumor was found in the surgical resection specimen. After radiotherapy, trastuzumab medication was initiated. To date, there is no evidence of local recurrence or distant metastases during her 24 months follow-up. The newborn is on close neurohabilitation folow-up due to the evidence of generalized muscle dystonia. Had the patient accepted chemotherapy, the damage of the newborn baby would have been avoidable