Ovarian cancer: Autologous immunotherapy optimized by remote adjuvancy of a silicate-induced granuloma

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.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12509-12509
Author(s):  
E. M. Lasalvia-Prisco ◽  
E. Garcia-Giralt ◽  
S. Cucchi ◽  
J. Larrañaga ◽  
D. Wagner

12509 Background: In several peer review publications (Cancer Biol Ther 2003) our team has reported a procedure of cancer immunotherapy using an autologous thermostable hemoderivative vaccine (ATHV) with anti-progressive tumor effect in metastatic malignant disease from different primary tumors including prostate cancer. Last year (ASCO Meeting 2005) we have reported that the tolerance break for tumor associated antigens through the interference with CD4+CD25+ regulatory cells is a component of the mechanism of action of the ATHV antitumoral effect. Therefore, we have intended to optimize this autologous immunotherapy adding to the procedure different steps of immune-tolerance blockage selected due to their proven efficacy in pre-clinical models and their feasibility in the frame of ATHV technology. In this study we report the results in prostate cancer when the adjuvant step added was the translational knowledge the tolerance blockage by IDO-inhibition through 1-Methyl-Tryptophane or 1-MT (Munn DH et al J Exp Med 1999). Methods: Thirty metastasic prostate cancer patients, hormone and chemotherapy resistant, Performance Status ≤ 2 and PSA progressing serum level, were included in this institutional-IRB approved phase I/II trial. The patients were randomized in 3 groups submitted to 3 different treatments: I, only sympthomatic; II, the previously reported ATHV and III, ATHV + simultaneous s.c. 1-MT. Tumor size increase (tumor growth) measured according RECIST was registered in each case. Mean difference in the 3 groups was statistically assessed (Student’s t-test). Tryptophane to Kynurenine conversion was tested to assess IDO inhibition. Results: Tumor growth was significantly slower in Group II and III than in Group I (p<0.01 and p<0.005). Tumor growth was also significantly slower in Group III than in Group II (p<0.02). IDO-inhibition was confirmed only in Group III. No relevant toxicities were detected. Conclusions: These results support that additional tolerance break by IDO-inhibition optimizes the tumor growth inhibition through immunotherapy with an autologous thermostable hemoderivative vaccine. No significant financial relationships to disclose.


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.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14580-e14580
Author(s):  
R. Hariprasad ◽  
L. Kumar ◽  
S. Kumar ◽  
N. Bhatla ◽  
S. Thulkar ◽  
...  

e14580 Background: Survival of patients with advanced epithelial ovarian cancer (EOC) with initial suboptimal debulking surgery (residual disease (>1 cm) and those with recurrent EOC is poor. We used EGFR inhibitor gefitinib for maintenance and analyzed data on safety and toxicity. Methods: Between Nov. 2004 and Dec. 2008, Patients who achieved complete response (CR) following six cycles of paclitaxel and carboplatin received gefitinib as (Group I). Similarly, patients with recurrent EOC who achieved CR following six cycles of salvage CT received gefitinib (Group II). Both groups received gefitinib 250 mg once daily till evidence of relapse. Patients were examined every month and toxicity (CTC version II) was recorded. Serum CA-125 was done once in 2 months and CAT scan of abdomen & pelvis every 6 month. The study was approved by Institute Ethics Committee and informed written consent was obtained from each patient. Results: A total of 48 patients (median age 47 years, range 23 to 63) have been recruited. Group I: 17 subjects and Group II 31 patients (1st relapse- 13, 2nd- 9, 3rd -6 & 4th relapse in 3 patients). The mean duration of gefitinib treatment is 8.77 months (Gp-I: 14.4 months, Gp-II: 5.68 months). Toxicity was mainly in the form of skin rash & diarrhea. Skin rash: 16 patients (33.3%); Group I - 8 (grade I-2, II-4, III-3,) & Group II - 8 patients (grade I-3,II-4,III-1). Diarrhea: 12 patients (25%); Group I-3, group II- 9) all grade I. Two patients had both skin rashes and diarrhea. No pulmonary or hematological toxicity was observed. Currently, 13 patients are on gefitinib (mean duration of treatment 12.6 months); in 34 patients gefitinib has been discontinued due to relapse and in 1 patient due to grade III skin rashes over face. Among 18 patients with skin toxicity, 8 continue to be disease-free compared to 6 of 30 without skin toxicity (p=0.07). Conclusions: Gefitinib was tolerated well with mild toxicities limited to skin and GIT. Correlations between EGFR expressions vs. response may help to identify patients likely to benefit from gefitinib therapy. No significant financial relationships to disclose.


2004 ◽  
Vol 22 (17) ◽  
pp. 3507-3516 ◽  
Author(s):  
Jonathan S. Berek ◽  
Peyton T. Taylor ◽  
Alan Gordon ◽  
Mary J. Cunningham ◽  
Neil Finkler ◽  
...  

Purpose To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study. Patients and Methods Patients with stage III/IV ovarian cancer who had a complete clinical response to primary treatment were randomly assigned to oregovomab or placebo administered at weeks 0, 4, and 8, and every 12 weeks up to 2 years or until recurrence. The primary end-point was time to relapse (TTR). Results One hundred forty-five patients were treated with oregovomab (n = 73) or placebo (n = 72). For the population overall, median TTR was not different between treatments at 13.3 months for oregovomab and 10.3 months for placebo (P = .71). Immune responses were induced in most actively treated patients. This was associated with prolonged TTR. Quality of life was not adversely impacted by treatment. Adverse events were reported with similar frequency in oregovomab and placebo groups, indicating a benign safety profile. A long-term survival follow-up is ongoing. Cox analysis of relapse data identified significant factors: performance status, CA-125 before third cycle, and baseline CA-125. Further evaluation identified a subpopulation with favorable prognostic indicators designated as the successful front-line therapy (SFLT) population. For the SFLT population, TTR was 24.0 months in the oregovomab group compared with 10.8 months for placebo (unadjusted hazard ratio of 0.543 [95% CI, 0.287 to 1.025]), a hypothesis-generating observation. Conclusion Consolidation therapy with oregovomab did not significantly improve TTR overall. A set of confirmatory phase III studies has been initiated to determine whether the SFLT population derives benefit from oregovomab treatment.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16579-e16579
Author(s):  
A. Chudecka-Glaz ◽  
D. Zielinska ◽  
I. Rzepka-Górska

e16579 Background: CA 125 is known and useful marker in diagnosis and follow up of patients with ovarian cancer. But there is only a few study about YKL-40 and its usefulness in these patients. The aim of our study was to compare the serum levels of YKL-40 and CA 125 in patients with active phase of ovarian cancer disease (during diagnosis and recurrence). Methods: We analyzed 58 women with ovarian cancer hospitalized and treatment in period from January 2006 to March 2008. Group I - 42 patients constituted women with actually diagnosed ovarian cancer and group II women with recurrence of ovarian cancer. Results: Mean value of YKL-40 in patients with just diagnosed ovarian cancer was 181 ng/mL (16.42–766.1 ng/ml). Mean value of YKL-40 in patients with the recurrent of ovarian cancer was 122.38 ng/mL (9.47–389.22 ng/mL). CA 125 respectively 729.58 U/mL (10.62–4882.1 U/mL) and 579.15 /mL (5.38–6000 U/mL). When the cut-off level for YKL-40 was set at 130 ng/mL we found elevated serum levels in 50% of group I and 38% of group II. Respectively in group I we found 73% elevated values of YKL-40 and 44% in group II when the cut-off level was set at 61 ng/mL. In patients with diagnosed ovarian cancer percentage of elevated CA 125 serum value was 90% and 55% in recurrent ovarian cancer (cut-off level -35 U/mL). Conclusions: Significance of YKL-40 tumor marker in ovarian cancer diagnosis seems to be less then known CA 125 antigen. No significant financial relationships to disclose.


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.


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.


2015 ◽  
Vol 18 (3) ◽  
pp. 098
Author(s):  
Cem Arıtürk ◽  
Serpil Ustalar Özgen ◽  
Behiç Danışan ◽  
Hasan Karabulut ◽  
Fevzi Toraman

<p class="p1"><span class="s1"><strong>Background:</strong> The inspiratory oxygen fraction (FiO<sub>2</sub>) is usually set between 60% and 100% during conventional extracorporeal circulation (ECC). However, this strategy causes partial oxygen pressure (PaO<sub>2</sub>) to reach hyperoxemic levels (&gt;180 mmHg). During anesthetic management of cardiothoracic surgery it is important to keep PaO<sub>2</sub> levels between 80-180 mmHg. The aim of this study was to assess whether adjusting FiO<sub>2</sub> levels in accordance with body temperature and body surface area (BSA) during ECC is an effective method for maintaining normoxemic PaO<sub>2</sub> during cardiac surgery.</span></p><p class="p1"><span class="s1"><strong>Methods:</strong> After approval from the Ethics Committee of the University of Acıbadem, informed consent was given from 60 patients. FiO<sub>2</sub> adjustment strategies applied to the patients in the groups were as follows: FiO<sub>2</sub> levels were set as 0.21 × BSA during hypothermia and 0.21 × BSA + 10 during rewarming in Group I; 0.18 × BSA during hypothermia and 0.18 × BSA + 15 during rewarming in Group II; and 0.18 × BSA during hypothermia and variable with body temperature during rewarming in Group III. Arterial blood gas values and hemodynamic parameters were recorded before ECC (T1); at the 10th minute of cross clamp (T2); when the esophageal temperature (OT) reached 34°C (T3); when OT reached 36°C (T4); and just before the cessation of ECC (T5).</span></p><p class="p1"><span class="s1"><strong>Results:</strong> Mean PaO<sub>2</sub> was significantly higher in Group I than in Group II at T2 and T3 (<em>P</em> = .0001 and <em>P</em> = .0001, respectively); in Group I than in Group III at T1 (<em>P</em> = .02); and in Group II than in Group III at T2, T3, and T4 <br /> (<em>P</em> = .0001 for all). </span></p><p class="p1"><span class="s1"><strong>Conclusion: </strong>Adjustment of FiO<sub>2</sub> according to BSA rather than keeping it at a constant level is more appropriate for keeping PaO<sub>2</sub> between safe level limits. However, since oxygen consumption of cells vary with body temperature, it would be appropriate to set FiO<sub>2</sub> levels in concordance with the body temperature in the <br /> rewarming period.</span></p>


2016 ◽  
pp. 108-111
Author(s):  
T.F. Tatarchuk ◽  
◽  
D.G. German ◽  

The article presents the comparative analysis of the state of the cervix in women with endometrial polyps and micropolyps. Patients and methods. The study involved 130 patients aged 18-35 years: 70 patients with endometrial polyps (group I), 30 patients with micropolyps (group II) and 30 patients of the control group (group III). Results. According to the anamnesis of women in the I group were significantly more frequent diseases of the cervix, which corrected physical surgery methods, in particular cryodestruction. In group II, the representatives of these indicators were similar to healthy. Normal colposcopic picture met significantly less frequently in patients and I, and II group. The differences in the incidence of HPV high oncogenic risk in all groups were not statistically significant. Conclusion. Destructive methods used in the detection of any changes in the cervix are often overly aggressive, form scars and contributing to inflamaciones process. In the chain of events leading to the formation of PE, cervical pathology and its correction can take the basic place. Key words: endometrial polyp, micropolyps, chronic endometritis, uterine cervix, colposcopy.


Author(s):  
Г.В. ШИРЯЕВ ◽  
Ю.Г. ТУРЛОВА ◽  
Г.С. НИКИТИН

Изучено влияние кормовой добавки в форме индивидуальных болюсов Метраболь на возможность снижения негативного влияния субклинического кетоза (СКК) и результативность искусственного осеменения высокопродуктивных молочных коров в посттранзитный период. Животные были подобраны по принципу условных аналогов и разделены на 3 группы в зависимости от концентрации β-оксимасляной кислоты в их крови. В I группе (n=18) у коров не было СКК, концентрация кислоты составляла <1,0 ммоль/л, во II группе (n=21) у животных зарегистрирован СКК, концентрация кислоты — 1,0…1,4 ммоль/л. С целью поиска решения по снижению негативного влияния СКК на репродуктивные показатели была сформирована III группа коров, переболевших СКК (n=24) с концентрацией β-оксимасляной кислоты в крови 1,0…1,4 ммоль/л, но с использованием болюсов, применяемых для ускоренного восстановления репродуктивной функции коров после отела. Важной составляющей опыта явилось то, что к моменту гормональной синхронизации у коров всех 3 групп фиксировалось отсутствие СКК (снижение β-оксимасляной кислоты до уровня <1,0 ммоль/л). Для синхронизации полового цикла выбрана схема Пресинх-овсинх. Установлено, что гормональная синхронизация животных, перенесших СКК, в сравнении со здоровыми, не позволяет снизить негативное влияние данного нарушения обмена веществ. Во II группе у животных зафиксированы самые низкие репродуктивные показатели (количество использованных доз; индекс осеменения, сервис-период; время от первого до успешного осеменения; результат первичного осеменения; количество животных, осемененных 3 и более раз). В III группе применение болюсов позволило, в сравнении с животными II группы, не только избежать отрицательного воздействия СКК, но и превзойти по изучаемым параметрам животных из I группы. The effect of the feed additive in the form of individual boluses Metrabol on the possibility of reducing the negative effect of subclinical ketosis (CCK) and the effectiveness of artificial insemination of highly productive dairy cows in the post-transit period was studied. The animals were selected according to the principle of conditional analogs and divided into 3 groups depending on the concentration of β-hydroxybutyric acid in their blood. In group I (n=18), the cows did not have SSC, the acid concentration was <1.0 mmol/L, in group II (n=21), SSC was registered in animals — 1.0...1.4 mmol / L. In order to find a solution to reduce the negative effect of CCB on reproductive indices, a group III of cows was formed who had CCB (n = 24) with a concentration of β-hydroxybutyric acid in their blood of 1.0...1.4 mmol/L, but using boluses, used to accelerate the restoration of the reproductive function of cows after calving. An important component of the experiment was that by the time of hormonal synchronization, cows of all 3 groups had no SSC (decrease in β-hydroxybutyric acid to a level of <1.0 mmol/L). To synchronize the sexual cycle, the Pressinh-ovsinh scheme was chosen. It was found that hormonal synchronization of animals that underwent SSC, in comparison with healthy ones, does not allow reducing the negative effect of this metabolic disorder. In group II, animals had the lowest reproductive indices (number of doses used; insemination index, service period; time from first to successful insemination; result of primary insemination; number of animals inseminated 3 or more times). In group III, the use of boluses made it possible, in comparison with animals of group II, not only to avoid the negative effect of SSC, but also to surpass the animals from group I in terms of the studied parameters.


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