Endometrial Carcinoma Presenting as Vasculitic Sensorimotor Polyneuropathy

Paraneoplastic syndromes (PNS) are a heterogeneous group of symptoms which are indirectly caused by primary or metastatic tumor. Paraneoplastic polyneuropathy (PNP) is mostly related to small cell lung cancer (5%), prostate, gastric, and breast cancer. Only sporadic cases have been reported to be associated with endometrial cancer. We present a case of a premenopausal woman with severe vasculitic, asymmetric sensorimotor polyneuropathy that developed in conjunction with an endometrial carcinoma responding to surgical therapy of primary tumor combined to steroid therapy. Neurological symptoms such as asymmetrical sensorimotor deficits and painful paresthesias are suspicious when they occur in otherwise healthy women with no medical history. The phenomenon of a paraneoplastic syndrome can point to an underlying malignancy and can be used as marker of progression or regression of the tumor. Due to the rarity of PNP, there is no standard treatment. Recommended therapy is stage-adjusted treatment of the primary tumor

Massive uterine fibroid: a diagnostic dilemma: a case report and review of the literature

Background Fibroids of the uterus are the most common benign pelvic tumors in women worldwide. Their diagnosis is usually not missed because of the widespread and well-established use of ultrasound in gynecological clinics. Hence, the development of an unusually large myoma is a rare event, particularly in first-world countries such as Germany. It is even more uncommon that a myoma is misdiagnosed as a dietary failure. Case presentation Herein, we report the case of a Caucasian woman with a giant fibroid that reached a size of over 50 cm, growing slowly over the past 15 years, and was misdiagnosed as abdominal fat due to weight gain. We aim to discuss the factors that lead to the growth of such a huge tumoral mass, including misdiagnosis and treatment, and the psychological impact. Through this case, we intend to increase the awareness among general physicians and gynecologists. Although menstrual disorders incorporate several pathologies, adequate assessment remains the primary responsibility of health care providers. A literature review revealed approximately 60 cases of giant uterine fibroids. Conclusion The use of clinical and diagnostic devices, especially ultrasound, in this case, is indispensable. In conclusion, the growth of a giant fibroid can have disastrous effects on a woman's health, including surgical trauma and psychological issues

Galectin-3 Released by Pancreatic Ductal Adenocarcinoma Suppresses γδ T Cell Proliferation but Not Their Cytotoxicity

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment with a dense desmoplastic stroma. The expression of β-galactoside-binding protein galectin-3 is regarded as an intrinsic tumor escape mechanism for inhibition of tumor-infiltrating T cell function. In this study, we demonstrated that galectin-3 is expressed by PDAC and by γδ or αβ T cells but is only released in small amounts by either cell population. Interestingly, large amounts of galectin-3 were released during the co-culture of allogeneic in vitro expanded or allogeneic or autologous resting T cells with PDAC cells. By focusing on the co-culture of tumor cells and γδ T cells, we observed that knockdown of galectin-3 in tumor cells identified these cells as the source of secreted galectin-3. Galectin-3 released by tumor cells or addition of physiological concentrations of recombinant galectin-3 did neither further inhibit the impaired γδ T cell cytotoxicity against PDAC cells nor did it induce cell death of in vitro expanded γδ T cells. Initial proliferation of resting peripheral blood and tumor-infiltrating Vδ2-expressing γδ T cells was impaired by galectin-3 in a cell-cell-contact dependent manner. The interaction of galectin-3 with α3β1 integrin expressed by Vδ2 γδ T cells was involved in the inhibition of γδ T cell proliferation. The addition of bispecific antibodies targeting γδ T cells to PDAC cells enhanced their cytotoxic activity independent of the galectin-3 release. These results are of high relevance in the context of an in vivo application of bispecific antibodies which can enhance cytotoxic activity of γδ T cells against tumor cells but probably not their proliferation when galectin-3 is present. In contrast, adoptive transfer of in vitro expanded γδ T cells together with bispecific antibodies will enhance γδ T cell cytotoxicity and overcomes the immunosuppressive function of galectin-3

Combined PARP and Dual Topoisomerase Inhibition Potentiates Genome Instability and Cell Death in Ovarian Cancer

Although ovarian cancer is a rare disease, it constitutes the fifth leading cause of cancer death among women. It is of major importance to develop new therapeutic strategies to improve survival. Combining P8-D6, a novel dual topoisomerase inhibitor with exceptional anti-tumoral properties in ovarian cancer and compounds in preclinical research, and olaparib, a PARP inhibitor targeting DNA damage repair, is a promising approach. P8-D6 induces DNA damage that can be repaired by base excision repair or homologous recombination in which PARP plays a major role. This study analyzed benefits of combining P8-D6 and olaparib treatment in 2D and 3D cultures with ovarian cancer cells. Measurement of viability, cytotoxicity and caspase activity were used to assess therapy efficacy and to calculate the combination index (CI). Further DNA damage was quantified using the biomarkers RAD51 and γH2A.X. The combinational treatment led to an increased caspase activity and reduced viability. CI values partially show synergisms in combinations at 100 nM and 500 nM P8-D6. More DNA damage accumulated, and spheroids lost their membrane integrity due to the combinational treatment. While maintaining the same therapy efficacy as single-drug therapy, doses of P8-D6 and olaparib can be reduced in combinational treatments. Synergisms can be seen in some tested combinations. In summary, the combination therapy indicates benefits and acts synergistic at 100 nM and 500 nM P8-D6

Mucinous Cystic Neoplasm of Pancreas in a Pregnant Woman Presenting with Severe Anemia and Gastric Bleeding: Case Report and Review of the Literature

Mucinous cystic neoplasms of the pancreas are uncommon and especially their occurrence during pregnancy is an extremely rare event which necessitates an individualized and interdisciplinary management. A 33-year old woman was referred to our department during her third trimester of pregnancy (34th week of gestation) with severe anemia and tarry stools. Based on gastroscopic findings, our interdisciplinary team suspected a gastrointestinal stromal tumor and therefore indicated a prompt delivery via cesarean section completed with an oncological resection of the neoplasm. Histological examination subsequently showed a mucinous cystic neoplasm of the pancreas with no evidence of malignancy. To review the prevalence of mucinous cystic neoplasms and to discuss diagnosis and treatment during pregnancy. Moreover, we critically value the indication of preterm delivery and the oncological procedure in the perspective of outcome for mother and infant. A bleeding gastrointestinal tumor during pregnancy represents a life-threatening risk for mother and infant and requires an immediate interdisciplinary treatment. The urgency and radicality of the therapy should be adapted according to individual findings. As our patient's tumor was suspected of having a malignant progression, an extensive surgical intervention was necessary

Подбор оптимального типа инсулина для использования в инсулиновой помпе

Проектирование инсулиновой помпы и выбор оптимального типа инсулина для людей с заболеванием сахарный диабет. В процессе исследования проводился аналитический обзор аналогов инсулина ультракороткого действия в помпе и написание программы для корректного ввода гормона-инсулина в организм человека.Projection of an insulinic pomp and the choice of optimum type of insulin for people with a disease a diabetes mellitus. In the course of the research the state-of-the-art review of analogs of insulin of ultrashort action in a pomp and writing of the program for correct input of hormone-insulin was carried out to a human body

ADAM17 Inhibition Increases the Impact of Cisplatin Treatment in Ovarian Cancer Spheroids

Chemotherapy resistance is a major challenge in ovarian cancer (OvCa). Thus, novel treatment combinations are highly warranted. However, many promising drug candidates tested in two-dimensional (2D) cell culture have not proved successful in the clinic. For this reason, we analyzed our drug combination not only in monolayers but also in three-dimensional (3D) tumor spheroids. One potential therapeutic target for OvCa is A disintegrin and metalloprotease 17 (ADAM17). ADAM17 can be activated by chemotherapeutics, which leads to enhanced tumor growth due to concomitant substrate cleavage. Therefore, blocking ADAM17 during chemotherapy may overcome resistance. Here, we tested the effect of the ADAM17 inhibitor GW280264X in combination with cisplatin on ovarian cancer cells in 2D and 3D. In 2D, the effect on five cell lines was analyzed with two readouts. Three of these cell lines formed dense aggregates or spheroids (HEY, SKOV-3, and OVCAR-8) in 3D and the treatment effect was analyzed with a multicontent readout (cytotoxicity, viability, and caspase3/7 activation). We tested the combined therapy on tumor spheroids derived from primary patient cells. In 2D, we found a significant reduction in the half minimal (50%) inhibitory concentration (IC50) value of the combined treatment (GW280264X plus cisplatin) in comparison with cisplatin monotherapy in all five cell lines with both 2D readout assays (viability and caspase activation). In contrast, the combined treatment only showed an IC50 reduction in HEY and OVCAR-8 3D tumor spheroid models using caspase3/7 activity or CelltoxTM Green as the readout. Finally, we found an improved effect of GW280264X with cisplatin in tumor spheroids derived from patient samples. In summary, we demonstrate that ADAM17 inhibition is a promising treatment strategy in ovarian cancer