Immunomodulator in combination treatment of patients with ovarian cancer and its influence on DNA cytometric and immunological parameters.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18079-e18079
Author(s):  
Anna Yu. Ardzha ◽  
Ekaterina V. Verenikina ◽  
Elena Yu. Zlatnik ◽  
Vera P. Nikitina ◽  
Oksana E. Zhenilo ◽  
...  

e18079 Background: Immunotherapy in oncology has now proven effective, but standard approaches have not yet been defined. Ways to optimize and increase the effectiveness of treatment with immunomodulators, in particular interferon-gamma preparations, in such patients remain an urgent problem of gynecological oncology. The purpose of the study was to improve direct results of ovarian cancer treatment. Methods: The study included patients aged 50-77 years with inoperable ascitic ovarian cancer (verified by cytological examination of ascitic fluid), stage IIIC-IV, receiving neoadjuvant chemotherapy (CT) in combination with immunotherapy with interferon-gamma (IFNγ). Group I – 26 patients, CT with carboplatin (AUC-6), paclitaxel (175 mg/m2); group II – 22 patients, chemoimmunotherapy and intramuscular IFNγ (ingaron) - 500 000 IU on day 1, 1 million IU on days 2,3,5, a similar CT on day 4; group III – 24 patients, chemoimmunotherapy and intraperitoneal IFNγ (ingaron) - 500 000 IU on day 1, 1 million IU on days 2,3,5, a similar CT on day 4. Patients received on average 2-3 therapy cycles. Results: Progression was registered only in group I in 3.8%; complete response in patients without IFNγ – 7.8%, with intramuscular and intraperitoneal IFNγ – 27.3% and 37.5% (p≤0.05) respectively. Surgical treatment followed in all patients, with total surgeries in 87.5% of patients with intraperitoneal IFNγ. DNA cytometry showed the minimal number of aneuploid tumors in patients with intraperitoneal IFNγ (16.6%), while in patients without immunotherapy 38.4%. The DNA index statistically significantly decreased by 1.3 times in patients with intraperitoneal IFNγ compared with patients without IFNγ (1.11±0.01% vs. 1.4±0.05% respectively) (p≤0.05). Levels of CD3+CD4+ cells elevated by 1.2 times (from 36.2±1.6 to 44.9±3.78%, p≤0.05) in patients with intramuscular IFNγ; intraperitoneal IFNγ caused an increase in CD3+ lymphocytes by 1.3 times (from 62.1±2.8 to 77.9±2.94%, p < 0.05) and CD3+CD4+ by 1.4 times (from 36.2±1.6 to 50.6±5.9%, p≤0.05). Conclusions: Interferon-gamma (ingaron) in combination with CT improves direct results of the treatment; intraperitoneal injections of interferon-gamma demonstrated better outcomes and tolerance confirmed by immunological and DNA cytometric parameters.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9509-9509 ◽  
Author(s):  
David Walterhouse ◽  
Alberto S. Pappo ◽  
Jane L Meza ◽  
John C. Breneman ◽  
Andrea Anita Hayes-Jordan ◽  
...  

9509 Background: Intergroup Rhabdomyosarcoma Study (IRS) trials showed improved survival with VAC compared with VA for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II ERMS (see table). In COG ARST0331, we hypothesized that VA in combination with lower doses of C (total cumulative dose=4.8 g/m2) would produce the benefit of IRS-IV VAC with less toxicity for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II low-risk ERMS. Methods: This single arm, non-inferiority, phase III study enrolled newly diagnosed patients with Stage 1 Group III (non-orbit) ERMS or Stage 3 Group I/II ERMS onto Subset 2. Therapy was 4 cycles of VAC followed by 12 cycles of VA over 46 weeks (total cumulative doses: V=54 mg/m2, A=21.6 mg/m2, C=4.8 g/m2). The radiation therapy dose was 36 Gy for Group IIA patients, 41.4 Gy for Group IIB/C patients, and 50.4 Gy for Group III patients. From 2004–2008 girls with Group III vaginal RMS did not receive radiotherapy if a complete response was achieved with chemotherapy with or without delayed resection. The primary endpoint was failure-free survival (FFS), and results were compared with a fixed expected outcome. Results: With a median follow-up of 3.0 yrs, we observed 16 failures vs. 7.8 expected failures. Estimated 3-yr FFS was 63% (95% CI: 46%, 75%) (n=60), and overall survival (OS) was 84% (95% CI: 68%, 93%). Estimated 3-yr FFS was 46% (95% CI: 23%, 67%) for girls with non-bladder genitourinary tract ERMS (n=21) and 75% (95% CI: 53%, 88%) for all other Subset 2 patients (n=39). Conclusions: We observed suboptimal FFS of patients with Subset 2 low-risk RMS using reduced total cyclophosphamide (4.8 g/m2). Results were complicated by the choice of no radiation therapy for girls with vaginal tumors. Future studies for low-risk RMS Subset 2 patients could investigate a dose of C between 4.8 and 26.4 g/m2 with VA and local radiotherapy. [Table: see text]


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12515-12515
Author(s):  
E. Garcia-Giralt ◽  
E. Lasalvia-Prisco ◽  
S. Cucchi ◽  
E. Lasalvia-Galante ◽  
J. Vazquez ◽  
...  

12515 Background: Advanced ovarian cancer has been included in several studies about an immunotherapy procedure using an Autologous Thermostable Hemoderivative Vaccine (ATHV) with anti-progressive tumor effect in metastatic malignant disease from different primary tumors (Cancer Biol Ther 2003). Like in most cancer vaccines, the net anti-tumoral effect of ATHV has low intensity despite the addition of several adjuvant steps: immune response enhancement by GM-CSF, immune tolerance break by cyclophosphamide or interference with CD4+CD25+ regulatory cells (E. Lasalvia-Prisco et al. ASCO 2003–2005). The inclusion of another adjuvant immunomodulatory step to ATHV in patients with advanced ovarian cancer was explored in this study. The tested adjuvancy was the local and remote immune-stimulation elicited by a subcutaneous silicate-granuloma (SSG), a phenomenon well proven in preclinical models (RM Fauve et al. Immune Lett 1987; E Fontan et al Proc Nat Acad of Sci 1983). Methods: Twenty four metastasic ovarian cancer patients, chemotherapy resistant, performance status ≤ 2 and CA-125 progressing serum level, were included in this institutional-IRB approved phase I/II trial. The patients were 3-group randomized, submitted to 3 different treatments: I only sympthomatic; II the previously reported ATHV and III ATHV + SSG. Tumor Growth was assessed in each case by the tumor size increase (RECIST measured). Mean difference in the 3 groups was statistically assessed (Student’s test). Results: Tumor Growth was slower in Group II and III than in Group I (p<0.02, p<0.005). Tumor growth was slower in Group III than in Group II (p<0.02). No relevant toxicities were detected. Conclusions: The results support that in advanced ovarian cancer an additional subcutaneous silicate granuloma as adjuvant agent optimizes the tumor growth inhibition through immunotherapy with an autologous thermostable hemoderivative vaccine. The bypass of the immune-ignorance could be discussed as its mechanism of action. No significant financial relationships to disclose.


Author(s):  
Madhuri Boggiti

Abstract: Ovarian cancer is the deadliest type of cancer in women. It is often presented at an advanced stage and has a poor prognosis. The current treatment methods for this tumor are not safe and have serious side effects. It has been suggested that the use of steroids for hormonal purposes is linked to the development of ovarian cancer. The current study aims to investigate the effects of cinnamaldehyde on these hormones. The objective of this study was to investigate the effects of cinnamaldehyde on the reproductive hormones of rats after being induced to develop ovarian cancer. Cinnamaldehyde is an active compound that has been used in Asia for over 4000 years. Cinnamaldehyde has different biological activities including antimicrobial, antiinflammatory, antiviral, antioxidant, antitumor were reported by many investigators. In the present study, animals were randomly allocated into VI groups: Group -I served as a control with normal water and group-II was drug control (50 mg/kg b. w) rats received only cinnamaldehyde orally for 36 weeks. The rats in group III were given a single dose of 7,12 Dimethyl benzanthracene (100 µg/rat) dissolved in 10 µL of sesame oil to surgically exposed left ovary and maintained up to 36 weeks to initiate ovarian carcinogenesis. Group IV rats received DMBA + cinnamaldehyde 50 mg/kg b. w (before starting the experiment and continued up to 24 weeks). Group V rats received DMBA + cinnamaldehyde 50 mg/kg b. w (25-36 weeks). Group VI rats received DMBA + cinnamaldehyde 50 mg/kg b. w (1-36 weeks). Serum levels of Estrogen, progesterone, LH, FSH were estimated using ELISA. The results showed that significant increase in serum level of Estrogen, LH, FSH, and decreased progesterone in only DMBA treated group when compared with control groups. Also, there was a significant decrease in serum levels of Estrogen, LH, FSH, and increased progesterone in cinnamaldehyde treated groups (dose-dependent) when compared to only DMBA treated group. The results of the present study suggested that cinnamaldehyde has anticancer activity and further investigations are needed for evaluating the anticancer potential and mechanism of its action. Keywords: Cinnamaldehyde, DMBA, Ovarian cancer, Reproductive hormones.


Author(s):  
Yu.M. SMIRNOVA ◽  
A.V. PLATONOV ◽  
Т.В. СЕДУНОВА ◽  
А.Г. КУДРИН

Изучили влияние уровня продуктивности коров на показатели естественной резистентности организма на 3 группах коров черно-пестрой породы, разделенных по уровню удоя за предыдущую лактацию методом сбалансированных групп. I группа включала животных с продуктивностью до 6000 кг, II от 6001 до 8000, III от 8001 кг и более. Был проведен анализ продуктивных и воспроизводительных качеств коров, а также изучены морфо-биохимические и иммунологические показатели крови, где определяли содержание общего белка, его фракций, фагоцитарную активность нейтрофилов. Установили, положительную взаимосвязь между продуктивностью животных за предыдущую лактацию и уровнем продуктивности за 100 дней последующей лактации. Наблюдается удлинение сервис-периода от 94 до 110 дней и количества доз на оплодотворение животных от 1,3 до 1,8. Рост молочной продуктивности влечет за собой снижение поглотительной способности нейтрофилов (фагоцитарное число, фагоцитарный индекс и фагоцитарная активность). У животных III группы в сухостойный период, и в период раздоя установлено снижение фагоцитарного числа по сравнению с показателями коров I и II групп. Во II группе отмечается наибольшее количество фагоцитирующих нейтрофилов к общему числу подсчитанных (23,67). Увеличение молочной продуктивности приводит к снижению содержания -глобулинов в крови сухостойных коров. Полученные данные свидетельствуют об обратной связи между естественной резистентностью организма и уровнем молочной продуктивности коров.We analyzed the influence of cows productivity level on indicators of organisms natural resistances in 3 groups of black pied cattle, divided according to the level of yield accumulated during previous lactation, through the method of balanced groups. Group I included animals with productivity level up to 600 kg, II from 6.001 kg to 8000 kg, III from 8001 kg and more. The analysis of productive and reproducible qualities of cows was conducted. Also, we studied morpho-biochemical and immunological parameters of blood, which determined the content of total protein, its fractions, phagocytic activity of neutrophils. We established a positive relationship between the productivity of animals during the previous lactation and the level of productivity during 100 days of subsequent lactation. There is an extension of the service period from 94 to 110 days and the number of doses for animals fertilization increased from 1.3 to 1.8. The growth of milk productivity entails a decrease in the absorption capacity of neutrophils (phagocytic number, phagocytic index, and phagocytic activity). Among animals of group III, during the dry and milking periods, a decrease, in comparison with the indicators of cows from groups I and II, of the phagocytic number was found. In group II, there is a highest number of phagocytic neutrophils in relation to its counted total number (23.67). The increase of milk productivity leads to a decrease of -globulins in the blood of dry cows. Obtained data indicate an inverse relationship between the natural resistance of the organism and the level of cows milk productivity.


2005 ◽  
Vol 15 (1) ◽  
pp. 26-31 ◽  
Author(s):  
V. Loizzi ◽  
C. Rossi ◽  
G. Cormio ◽  
A. Cazzolla ◽  
D. Altomare ◽  
...  

The purpose of this study was to investigate the clinical features of hepatic metastasis in patients with epithelial ovarian cancer. From 1998 to 2002, all women with hepatic metastasis from ovarian cancer were identified at the University of Bari. Twenty-nine patients identified included one having stage IIC, one stage IIIA, two stage IIIB, 17 stage IIIC, and eight stage IVB. Eight women had hepatic metastasis at the time of the diagnosis of ovarian cancer (group I), 10 patients had hepatic metastasis as first recurrence (group II), and 11 (group III) as a second relapse. The median survival from the time of liver metastasis diagnosis was 19 months in group I patients, 24 months in group II patients, and 10 months in group III patients. No statistical differences in survival were seen among the three groups (P = 0.7). Cell type, performance status at the time of the primary tumor diagnosis, number of hepatic lesions, the presence of other sites of disease at the time of hepatic metastasis, and platinum-based chemotherapy were significantly related to survival. Better performance status, serous cell-type tumor, single hepatic lesion, the absence of other sites of disease, and platinum-based chemotherapy are good prognostic factors.


Author(s):  
Deep Chilana ◽  
Bhawana Rastogi ◽  
Abhishake Kumar ◽  
Brig V.P. Singh ◽  
Richa Arora ◽  
...  

Background: In laparoscopic surgeries, insufflation with carbon dioxide triggers vagal afferents on the bowel and peritoneum which induces emesis by activating the vomiting center. It is hypothesized that combined antiemetics with different sites of activity would be more effective than one drug alone for the prophylaxis against PONV. So, the present study was planned to compare the efficacy of granisetron, dexamethasone and combination of granisetron with dexamethasone to prevent PONV.Methods: This randomized prospective double-blind study was performed on 120 patients, aged between 18 and 58 years of ASA physical status I and II of either sex undergoing laparoscopic surgeries under general anesthesia. Patients were randomized in three groups, group I (granisetrone 2 mg I.V.), group II (dexamethasone) 8 mg I.V., group III (granisetrone+dexamethasone) 2 mg+8 mg I.V. with 40 patients in each group. Complete response, incidence of nausea, vomiting, and rescue antiemetic were recorded at specified intervals.Results: A complete response (defined as no PONV and no need for another rescue antiemetic) was achieved in 75% of the patients given granisetron, 70% in dexamethasone and in 92.5% of the patients given granisetron plus dexamethasone (P <0.05). The overall cumulative incidences (0-24 hours) of PONV were 10 (25%) in the granisetron, 12 (30%) in the dexamethasone and 3 (7.5%) in the combination group. No difference in adverse events were observed in any of the groups.Conclusions: The prophylactic therapy of granisetron 2 mg plus dexamethasone 8 mg just before induction of anaesthesia is significantly effective in prevention of PONV in patients undergoing laparoscopic surgeries.


Author(s):  
K.K. SEKHRI ◽  
C.S. ALEXANDER ◽  
H.T. NAGASAWA

C57BL male mice (Jackson Lab., Bar Harbor, Maine) weighing about 18 gms were randomly divided into three groups: group I was fed sweetened liquid alcohol diet (modified Schenkl) in which 36% of the calories were derived from alcohol; group II was maintained on a similar diet but alcohol was isocalorically substituted by sucrose; group III was fed regular mouse chow ad lib for five months. Liver and heart tissues were fixed in 2.5% cacodylate buffered glutaraldehyde, post-fixed in 2% osmium tetroxide and embedded in Epon-araldite.


Author(s):  
Anton Bózner ◽  
Mikuláš Gažo ◽  
Jozef Dostál

It is anticipated that Japanese quail /Coturnix coturnix japonica/ will provide animal proteins in long term space flights. Consequently this species of birds is of research interest of international space program INTERCOSMOS. In the year 1987 we reported on an experiment /2/ in which the effect of chronic acceleration of 2 G hypergravitation, the hypodynamy and the simultaneous effect of chronic acceleration and the location in the centre of the turntable of the centrifuge on the protein fractions in skeletal muscles was studied. The ultrastructure of the heart muscle was now in this experiments examined as well.Japanese quail cockerels, aged 48 days were exposed to 2 G hypergravitation /group IV/ in a 6,4 m diameter centrifuge, to hypodynamy /group III/ and their combination /group V/, respectively for 6 days / Fig.1/. The hypodynamy in group III was achieved by suspending the birds in jackets without contact the floor. The group II was located in the centre ofthe turntable of the centrifuge. The control group I. was kept under normal conditions. The quantitative ultrastructure of myocard was evaluated by the methods of Weibel/3/ - this enables to determine the number, relative size and volume of mitochondria volume of single mitochondria, defficiency of mitochondrial cristae and volume of myofibrils.


1998 ◽  
Vol 80 (09) ◽  
pp. 393-398 ◽  
Author(s):  
V. Regnault ◽  
E. Hachulla ◽  
L. Darnige ◽  
B. Roussel ◽  
J. C. Bensa ◽  
...  

SummaryMost anticardiolipin antibodies (ACA) associated with antiphospholipid syndrome (APS) are directed against epitopes expressed on β2-glycoprotein I (β2GPI). Despite a good correlation between standard ACA assays and those using purified human β2GPI as the sole antigen, some sera from APS patients only react in the latter. This is indicative of heterogeneity in anti-β2GPI antibodies. To characterize their reactivity profiles, human and bovine β2GPI were immobilized on γ-irradiated plates (β2GPI-ELISA), plain polystyrene precoated with increasing cardiolipin concentrations (CL/β2GPI-ELISA), and affinity columns. Fluid-phase inhibition experiments were also carried out with both proteins. Of 56 selected sera, restricted recognition of bovine or human β2GPI occurred respectively in 10/29 IgA-positive and 9/22 IgM-positive samples, and most of the latter (8/9) were missed by the standard ACA assay, as expected from a previous study. Based on species specificity and ACA results, IgG-positive samples (53/56) were categorized into three groups: antibodies reactive to bovine β2GPI only (group I) or to bovine and human β2GPI, group II being ACA-negative, and group III being ACA-positive. The most important group, group III (n = 33) was characterized by (i) binding when β2GPI was immobilized on γ-irradiated polystyrene or cardiolipin at sufficient concentration (regardless of β2GPI density, as assessed using 125I-β2GPI); (ii) and low avidity binding to fluid-phase β2GPI (Kd in the range 10–5 M). In contrast, all six group II samples showed (i) ability to bind human and bovine β2GPI immobilized on non-irradiated plates; (ii) concentration-dependent blockade of binding by cardiolipin, suggesting epitope location in the vicinity of the phospholipid binding site on native β2GPI; (iii) and relative avidities approximately 100-fold higher than in group III. Group I patients were heterogeneous with respect to CL/β2GPI-ELISA and ACA results (6/14 scored negative), possibly reflecting antibody differences in terms of avidity and epitope specificity. Affinity fractionation of 23 sera showed the existence, in individual patients, of various combinations of antibody subsets solely reactive to human or bovine β2GPI, together with cross-species reactive subsets present in all samples with dual reactivity namely groups III and II, although the latter antibodies were poorly purified on either column. Therefore, the mode of presentation of β2GPI greatly influences its recognition by anti-β2GPI antibodies with marked inter-individual heterogeneity, in relation to ACA quantitation and, possibly, disease presentation and pathogenesis.


Author(s):  
Ahmed Mousa ◽  
Ossama M. Zakaria ◽  
Mai A. Elkalla ◽  
Lotfy A. Abdelsattar ◽  
Hamad Al-Game'a

AbstractThis study was aimed to evaluate different management modalities for peripheral vascular trauma in children, with the aid of the Mangled Extremity Severity Score (MESS). A single-center retrospective analysis took place between 2010 and 2017 at University Hospitals, having emergencies and critical care centers. Different types of vascular repair were adopted by skillful vascular experts and highly trained pediatric surgeons. Patients were divided into three different age groups. Group I included those children between 5 and 10 years; group II involved pediatrics between 11 and 15 years; while children between 16 and 21 years participated in group III. We recruited 183 children with peripheral vascular injuries. They were 87% males and 13% females, with the mean age of 14.72 ± 04. Arteriorrhaphy was performed in 32%; end-to-end anastomosis and natural vein graft were adopted in 40.5 and 49%, respectively. On the other hand, 10.5% underwent bypass surgery. The age groups I and II are highly susceptible to penetrating trauma (p = 0.001), while patients with an extreme age (i.e., group III) are more susceptible to blunt injury (p = 0.001). The MESS has a significant correlation to both age groups I and II (p = 0.001). Vein patch angioplasty and end-to-end primary repair should be adopted as the main treatment options for the repair of extremity vascular injuries in children. Moreover, other treatment modalities, such as repair with autologous vein graft/bypass surgery, may be adopted whenever possible. They are cost-effective, reliable, and simple techniques with fewer postoperative complication, especially in poor/limited resources.


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