ANTIMICROBIAL THERAPY DURING CANCER TREATMENT: A CASE REPORT

Introduction. Penile cancer (pc) is a rare cancer. The standardized incidence rate of pc in russia is 0.82 cases per 100,000 males. On average, 58 % of patients (20–96 %) with pc have a local infection process: tumor decay, the presence of erosion, tumor ulceration, inflammatory changes in regional lymph nodes, etc. During hospitalization nosocomial pathogens may be possible causes of infection in ulcerative lesions.The aim of the study was to present the results of the treatment of tumor ulcer in a patient with penile cancer infected with multiresistant acinetobacter baumannii and klebsiella pneumoniae.Material and methods. We present a clinical observation of 54-year-old patient diagnosed with penile cancer pt4n3m0, with ulceration of the tumor, localized at the root of the penis and ulceration of metastatic lymph nodes in the left inguinal region and subsequent infection with highly resistant nosocomial microorganisms.Results. The patient received 6 courses of paclitaxel, ifosfamide and cisplatin with clinical effect, such as significant reduction of the tumor and therapeutic pathomorphosis of 3-rd degree. Then ileo-inguinal lymphadenectomy was performed on the left. A few months later the tumor continued to grow in the left groin area. During the 2nd line of chemotherapy (cisplatin, docetaxel and capecitabine), the patient had grade iii–iv neutropenia, febrile neutropenia. High fever and localized infection in the area of tumor ulceration with multiresistant hospital microorganisms was detected. Combined antibiotic therapy had temporary effect. After isolation of multiresistant carbapenemresistant k. Pneumoniae from the ulcer, the patient was prescribed ceftazidim/avibactam 2.5 g 3 times a day. Clinical effect, such as defervescence and significant reduction of the ulceration zone was seen subsequently.Conclusion. Etiotropic antibacterial therapy of the infected tumor ulcer resulted in a significant reduction in the manifestation of the infection process, allowing antitumor therapy to be continued, as well as surgery to be performed.

Oncolytic Adenovirus in Cancer Immunotherapy

Tumor-selective replicating “oncolytic” viruses are novel and promising tools for immunotherapy of cancer. However, despite their first success in clinical trials, previous experience suggests that currently used oncolytic virus monotherapies will not be effective enough to achieve complete tumor responses and long-term cure in a broad spectrum of cancers. Nevertheless, there are reasonable arguments that suggest advanced oncolytic viruses will play an essential role as enablers of multi-stage immunotherapies including established systemic immunotherapies. Oncolytic adenoviruses (oAds) display several features to meet this therapeutic need. oAds potently lyse infected tumor cells and induce a strong immunogenic cell death associated with tumor inflammation and induction of antitumor immune responses. Furthermore, established and versatile platforms of oAds exist, which are well suited for the incorporation of heterologous genes to optimally exploit and amplify the immunostimulatory effect of viral oncolysis. A considerable spectrum of functional genes has already been integrated in oAds to optimize particular aspects of immune stimulation including antigen presentation, T cell priming, engagement of additional effector functions, and interference with immunosuppression. These advanced concepts have the potential to play a promising future role as enablers of multi-stage immunotherapies involving adoptive cell transfer and systemic immunotherapies.

Gigantic Dermatofibrosarcoma Protuberans of the Scalp with Fibrosarcomatous Transformation

Here we are reporting this rare and unfortunate presentation of Dermatofibrosarcoma protuberans (DFSP) of the scalp. The patient was a 30 years old male from a remote area, with history of 4 previous surgical interventions. He was transferred directly to our surgical ICU with septicemia; anuria; severe anemia; and respiratory failure. Patient had a massive fungating infected tumor on his scalp. CT scan shown a subcutaneous scalp tumor with maximum diameter of 45 cm and adherence to occipital bone but no intracranial invasion. The tumor kept bleeding whenever the blood pressure maintained to optimum level. Patient had to be taken to the O.R joined with Neurosurgeon in attempt of surgical control of bleeding by elevating the tumor from its bed. Unfortunately, patient collapsed intra-operatively and despite extensive attempts of resuscitation by Anesthesia team, patient could not be salvaged. The final pathology was DFSP with malignant sarcomata’s transformation. To the best of our knowledge this is the largest reported DFSP case in the Head and Neck region, in English literature.

Adenovirus infection promotes the formation of glioma stem cells from glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

Background Glioma stem cells (GSCs) are glioma cells with stemness and are responsible for a variety of malignant behaviors of glioma. Evidence has shown that signals from tumor microenvironment (TME) enhance stemness of glioma cells. However, identification of the signaling molecules and underlying mechanisms has not been completely elucidated. Methods Human samples and glioma cell lines were cultured in vitro to determine the effects of adenovirus (ADV) infection by sphere formation, RT-qPCR, western blotting, FACS and immunofluorescence. For in vivo analysis, mouse intracranial tumor model was applied. Bioinformatics analysis, gene knockdown by siRNA, RT-qPCR and western blotting were applied for further mechanistic studies. Results Infection of patient-derived glioma cells with ADV increases the formation of tumor spheres. ADV infection upregulated stem cell markers and in turn promoted the capacities of self-renewal and multi-lineage differentiation of the infected tumor spheres. These ADV infected tumor spheres had stronger potential to form xenograft tumors in immune-compromised mice. GSCs formation could be promoted by ADV infection via TLR9, because TLR9 was upregulated after ADV infection, and knockdown of TLR9 reduced ADV-induced GSCs. Consistently, MYD88, as well as total STAT3 and phosphorylated (p-)STAT3, were also upregulated in ADV-induced GSCs. Knockdown of MYD88 or pharmaceutical inhibition of STAT3 attenuated stemness of ADV-induced GSCs. Moreover, we found that ADV infection upregulated lncRNA NEAT1. Knockdown of NEAT1 impaired stemness of ADV-induced GSCs. Lastly, HMGB1, a damage associated molecular pattern (DAMP) that triggers TLR signaling, also upregulated stemness markers in glioma cells. Conclusion ADV, which has been developed as vectors for gene therapy and oncolytic virus, promotes the formation of GSCs via TLR9/NEAT1/STAT3 signaling.

CHOP and IRE1α-XBP1/JNK signaling promote Newcastle Disease Virus induced apoptosis and benefit virus proliferation

ABSTRACTNewcastle disease virus (NDV) causes severe infectious disease in poultry, and selectively kills tumor cells by inducing apoptosis. In this report, we revealed the mechanisms underlying NDV-induced apoptosis via investigation of endoplasmic reticulum (ER) stress-related unfolded protein response (UPR) in HeLa cells. We found that NDV infection induced the expression of pro-apoptotic transcription factor CHOP via PKR-eIF2α pathway. Knock down and exogenous expression studies showed that CHOP promoted cell apoptosis by down-regulation of anti-apoptotic protein BCL-2 and MCL-1, promotion of pro-apoptotic JNK and p38 signaling, and suppression of pro-survival AKT signaling. Meanwhile, CHOP facilitated NDV proliferation. Furthermore, virus infection activated IRE1α, another ER stress sensor, thereby promoting the mRNA splicing of XBP1 and resulting in the translation of transcription factor XBP1s. XBP1s entered into cell nucleus, promoted the expression of ER chaperones and components of ER associated degradation (ERAD). Exogenous expression of XBP1s helped IBV proliferation, and silence of XBP1s reduced virus proliferation. Meanwhile, exogenous expression and knock down studies demonstrated that IRE1α activated pro-apoptotic JNK signaling, promoted apoptosis and inflammation. In conclusion, our current study demonstrates that the induction of CHOP and activation of IRE1α-XBP1/JNK signaling cascades promote apoptosis and benefit NDV proliferation.IMPORTANCEIt is well known that NDV kills host animal and tumor cells by inducing cell apoptosis. Although several studies investigate the apoptotic phenomena in NDV-infected tumor cells, the molecular mechanisms underlying this oncolytic virus induced apoptosis is not well understood yet. In this study, we focus on characterization of the ER stress responses in NDV-infected tumor cells, and find that virus induces apoptosis by up-regulation or activation of several unfolded protein responses (UPR) related transcription factors and signaling: such as ATF4, CHOP and XBP1s, and pro-apoptotic kinases (IRE1α, JNK, p38). Moreover, activation of these transcription factors and signaling cascades helps virus proliferation. Our study dissects the UPR induced apoptosis in NDV-infected tumor cells, and provides the evidence that UPR favors NDV proliferation.

Changes in cervical cancer course under the influence of HPV/chlamydia trachomatis co-infection.

e17018 Background: The purpose of the study was to analyze the effect of HPV/Chlamydia trachomatis co-infection on the hormonal status of tumor and visually unchanged cervical tissues in cervical cancer patients. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4) and prolactin (PRL) by the ELISA in tumors and visually unchanged cervical tissues of 49 patients with cervical cancer T1b-2aN0M0 with endophytic (25 patients) and exophytic (24 patients) patterns of tumor growth. 13 patients with endophytic tumors and 12 patients with exophytic ones were infected with HPV and Сhlamydia trachomatis (Ch.tr.). HPV infection was determined by Е7 protein expression, Ch.tr. – by IgG and IgА and antigen/DNA in ELISA and PCR. Intact cervical tissues obtained during hysterectomy from 22 non-infected women with endometrial cancer were used as the control. Results: Tumor tissues of the cervix without infection demonstrated increased levels of all sex steroids: estrogens by 3 times, androgens by 3.1 times and progestins by 1.8 times. Co-infected tissues were characterized by the sex-steroid imbalance. We observed reduced coefficients of estrogens to T and fT by 1.6 and 6 times, respectively, compared to intact tissues (most significant in a tumor with endophytic growth pattern) and an increase in the estrogens to P4 ratio by 1.5 times – only in endophytic growth pattern. Androgenic status in co-infected tumor tissues increased by 1.7 in endophytic and by 3.1 times in exophytic growth pattern. PRL level was increased only in co-infected tumors (by 2.5 times). Unchanged co-infected tissues, unlike non-infected samples, showed E2 increase by 2.6 times in exophytic and by 1.5 times in endophytic growth pattern, T increase by 1.6 times only in endophytic tumors and P4 decrease by 1.5 times and PRL increase by 1.8 times regardless the tumor growth pattern. Conclusions: Hormonal profile of both tumor and unchanged cervical tissues was dependent on HPV/Ch. tr. co-infection and tumor growth patterns. The changes could result from HPV and Ch. tr. interaction triggering malignant processes.