DNA cytometric parameters as prognostic factors of chemoimmunotherapy for ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17041-e17041
Author(s):  
Galina Andreevna Nerodo ◽  
Oleg Ivanovich Kit ◽  
Inna Arnoldovna Novikova ◽  
Anna Ardzha ◽  
Ekaterina V. Verenikina ◽  
...  

e17041 Background: The aim of the study was to analyze chemoimmunotherapy influence on DNA cytometric parameters in patients with ovarian cancer. Methods: The study included stage IIIC-IV ovarian cancer patients divided into two groups in dependence on the treatment: group A – 21 patients who did not receive neoadjuvant chemotherapy before surgery; group B – 24 patients who received neoadjuvant chemoimmunotherapy with intraperitoneal administration of interferon-gamma (ingaron) and the following surgery. The groups were identical in terms of the disease stages, age and general condition of patients. DNAs were analyzed in fresh tumor tissues using CycleTEST Plus DNA Reagent Kit (Becton Dickinson, USA). The data were processed using the ModFit LT program allowing analysis of ploidy and distribution of tumor cells in phases of the cell cycle. The proportion of cells with different DNA content in the histogram was calculated as a percentage of the total number of studied cells. Proliferation index (PI) was calculated as the total amount of tumor cells in S and G2+М phases of the cell cycle. Results: Full-volume surgery (panhysterectomy+omentectomy) was performed in 52.4% in group A and in 92% in group B, adnexectomy only – in 38.1% and 8%, respectively; exploratory surgeries were performed in group A only – 9.5%. During 2 years of the observation, recurrence in group A was found in 38% of patients, in group B – in 12.5%. Analysis of DNA cytometric parameters showed the minimal proliferation rates (percentage of cells in S phase) in group B – 12.6±2.3%, compared with 20.7±3.4% in group A. PI was lowest in group B – 13±2.7%, compared with group A – 22.4±3.3% (p≤0.05). Significant decrease in the DNA index by 1.3 times was noted in patients in group B in comparison with group A (1.11±0.01% and 1.4±0.05%, respectively) (p≤ 0.05). Conclusions: Thus,DNA cytometric parameters reflect the effectiveness of chemoimmunotherapy and can be used as prognostic factors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16558-e16558
Author(s):  
Inna Arnoldovna Novikova ◽  
Galina Nerodo ◽  
Anna Iurievna Mordan

e16558 Background: A ploidy of an average grade of aneuploidy cells and of proliferation index in ovarian tumor was studied. Methods: 21 patients with ovarian cancer of III-IV grades and 12 patients with acknowledged relapse of the disease aged from 46 to 67 to part in the research. We used CycleTEST PLUS DNA Reagent Kit (Becton Dickinson) for the analysis of DNA in the tumor’s tissues. Preparation of the tumor’s tissues was made with the use of disaggregating device BD Medimachine; after painting with propidium iodide (PI) we analyzed at flow cytofluorimeter BD Facs CantooII. Received data was processed with the help of computer program ModFit LT, allowing to analyze the ploidy and distribution of tumor’s cells according to phases of cellular cycle. Results: There was revealed the 2.5 times predominance of aneuploidy tumors over diploid in case of the relapse of the disease. The DNA index, different from 1.0, was registered in 83.3%, whereas there was noticed 33.3% primary ovarian tumors with aneuploidy content of DNA with predominance of diploidy tumors. There was noticed a tendency to the increase of aneuploidy cells during the relapse of the disease, where they made up 42.7±1.8%, whereas in primary ovarian tumors the share of aneuploidy cells was 40.4±1.6%. The index of proliferation of relapsing tumors was 1.8 times higher than this index of primary tumors, and made up 35.5±2.9 and 26.7±2.1 (p < 0.05). Conclusions: During the relapse of a tumor there is a predominance of aneuploidy tumors over diploid, the index of proliferation is higher in comparison with primary tumors.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Riffat Mehboob ◽  
Syed Amir Gilani ◽  
Amber Hassan ◽  
Sadaf ◽  
Imrana Tanvir ◽  
...  

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as “+3,” was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as “+2” (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining “+1” was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.


1984 ◽  
Vol 98 (2) ◽  
pp. 466-472 ◽  
Author(s):  
Y Kaneda ◽  
T Uchida ◽  
E Mekada ◽  
M Nakanishi ◽  
Y Okada

Ehrlich ascites tumor cells were found to be very insensitive to diphtheria toxin. We formed 37 hybrids from Ehrlich tumor cells and diphtheria toxin-sensitive human fibroblasts. The effects of diphtheria toxin on protein synthesis in those hybrids were examined. The hybrids were divided into three groups on the basis of toxin sensitivity. Group A hybrids were as sensitive to diphtheria toxin as human fibroblasts, Group C were as resistant as Ehrlich tumor cells, and Group B had intermediate sensitivity. Group A hybrids had diphtheria toxin-binding sites but Group B and C had no detectable binding sites. Elongation factor-2 of all the hybrids was susceptible to ADP-ribosylation by fragment A of diphtheria toxin. Cells of Group A and B became more sensitive to CRM 45 (cross-reacting material 45 of diphtheria toxin) after they were exposed to low pH (pH = 4.5). The resistance of Group C to CRM 45 was not affected by the same treatment. Group A and B hybrids and human fibroblasts had similar sensitivities to a hybrid toxin composed of wheat germ agglutinin and fragment A of diphtheria toxin, but Group C and Ehrlich tumor cells were resistant to this hybrid toxin. All the hybrids and Ehrlich tumor cells were more sensitive to a hybrid toxin composed of wheat germ agglutinin and subunit A of ricin than were human fibroblasts. On subcloning of Group B hybrids, one Group C hybrid was obtained, but no Group A hybrid. These facts suggest that Ehrlich ascites tumor cells differ from human fibroblasts in the expression of a factor(s) that is involved in entry of fragment A of diphtheria toxin into the cytoplasm after the toxin binds to its surface receptors.


1997 ◽  
Vol 17 (5) ◽  
pp. 467-470 ◽  
Author(s):  
Roel E. Reddingius ◽  
Alberdina W. De Boer ◽  
Cornelis H. Schröder ◽  
Johannes L. Willems ◽  
Leo A.H. Monnens

Objective To establish the effectivity of administration of erythropoietin intraperitoneally in a small amount of fluid in children with renal anemia on continuous ambulatory peritoneal dialysis (CAPD). Design Prospective study in which children with renal anemia on CAPD were treated with erythropoietin intraperitoneally, administered in a specially designed bag containing 50 mL NaCl 0.9%. Setting University hospital. Patients The patient population consisted of 9 children treated with CAPD and 1 treated with nightly intermittent peritoneal dialysis. The median age was 7.8 years (range 4.1 -15.2). Four of these children had not been treated with erythropoietin before (group A), and 6 had been treated with erythropoietin administered intraperitoneally in 250 mL of dialysis fluid (group B). Interventions Patients in group A started on a dose of approximately 300 units/kg per week (group A). Patients in group B received their previous dose. Do sage was adjusted to achieve a target hemoglobin level of 6.5 7.0 mmol/L (104 -112 g/L). Serum ferritin levels and transferrin saturation were monitored and iron supplementation was prescribed in the case of iron deficiency. Main outcome measures Weekly erythropoietin dose in relation to hemoglobin level. Results In group A, median hemoglobin level rose from 5.3 mmol/L (85 g/L) to 6.6 mmol/L (106 g/L) after 6 months of therapy, whereas the median erythropoietin dose decreased from 266 to 234 U/kg/week. In group B, hemoglobin levels remained stable and median erythropoietin dose decreased from 262 to 194 U/kg/week. One patient in this group, for unknown reasons, never responded to erythropoietin treatment. He was excluded from further analysis. In the remaining 5 patients the median cumulative erythropoietin dose was 3250 U/kg in the 3-month period prior to the start of the study and 2713 in the 3-month period starting 6 months after the beginning of the study. This difference of 17% was statistically significant using a Wilcoxon test (p < 0.05). Conclusion Intraperitoneal administration of erythropoietin in a small amount of dialysis fluid leads to a decrease in the required dose.


2007 ◽  
Vol 17 (2) ◽  
pp. 359-366 ◽  
Author(s):  
P. Harnett ◽  
M. Buck ◽  
P. Beale ◽  
A. Goldrick ◽  
S. Allan ◽  
...  

Gemcitabine and oxaliplatin have shown single-agent activity in relapsed ovarian cancer. This combination was used to determine response rates, time-to-event efficacy measures, and toxicity in patients with recurrent ovarian cancer. Patients with prior platinum-based chemotherapy who had measurable lesions and/or elevated CA-125 levels were identified as group A (platinum-refractory/platinum-resistant patients) and group B (platinum-sensitive patients). All patients received gemcitabine 1000 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days for up to eight cycles. Seventy-five patients (21 in group A and 54 in group B), with a median age of 58 years (range, 37–78), were enrolled. A median of six cycles (range, 1–8) was administered. By intent-to-treat analysis, 15 patients with measurable disease achieved partial response for an overall best response rate of 20.0% (9.5% in group A and 24.1% in group B). CA-125 response was observed in 48.4% patients (30.0% in group A and 57.1% in group B). Median time to progressive disease was 7.1 months (95% CI, 5.6–9.0 months) with 5.0 months in group A and 8.3 months in group B. Median overall survival was 17.8 months (95% CI, 12.9–21.3 months) with 9.2 months for group A and 20.0 months for group B. Major grade 3/4 toxicities were neutropenia (61.3%), leukopenia (24.0%), nausea (16.0%), and vomiting (22.7%). We conclude that the combination of oxaliplatin and gemcitabine is active in patients with recurrent ovarian cancer, but the regimen is unsatisfactory for further study due to modest response and relatively high toxicity.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5648-5648
Author(s):  
Sinem Nihal Esatoglu ◽  
Dilek Keskin ◽  
Muge Kutnu ◽  
Tugrul Elverdi ◽  
Ayse Salihoglu ◽  
...  

Abstract Introduction: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with variable clinical course. Several studies have been conducted to predict outcome in patients with CLL and also have been going on. A proliferation inducing ligand (APRIL) has been shown to involve in survival and resistance to apoptosis in CLL, and APRIL molecule has been investigated as a prognostic marker in CLL patients. However, there are limited and controversial data regarding APRIL and its impact on prognosis in CLL. We aimed to compare serum APRIL levels in CLL patients with those of age and gender matched healthy subjects, and to investigate the relationship between APRIL and the other common prognostic factors, and to determine whether serum APRIL levels predict time to first treatment in CLL. Methods: After ethical approval and informed consent were obtained, between May and December 2012, venous blood samples were driven from 96 CLL patients’ and 25 healthy controls’, and serum APRIL levels were measured by ELISA. Demographic data and the prognostic markers were obtained from the patients’ files, and patients have been followed for a minimum of 12 months. We tested the correlation between APRIL with the, clinical and biological parameters, and used the log rank test to compare their Kaplan Meier curves. Results: Patients were divided into three groups: Treatment naive (group A, n=49), chemotherapy receiving (group B, n=25) and who had previously received chemotherapy (group C, n=22). Median APRIL level was higher in group A (2.78 vs 1.29; p=0.034) and group C (3.54 vs 1.29; p=0.001) when compared to healthy controls, but was not different in group B (1.56 vs 1.29; p=0.3) (Figure 1). Serum APRIL level in group A was negatively correlated with hemoglobin levels (r=-0.298; p=0.037) and platelet counts (r=-0.321; p=0.025) whereas no correlation with age, Rai and Binet stages, lymphocyte counts, β2-microglobulin and CD38 levels were detected. Group A patients were also divided into 2 subgroups (APRIL levels low, n=20 and APRIL levels high, n=29) using median natural logarithm of serum APRIL level as cut off. April low and high subgroups were similar with respect to demographic data and prognostic factors. Median time to first treatment was not reached in the APRIL low group, but was 104 months in the APRIL high group (p=0.13, log-rank test). Conclusions: Among the treatment naive patients, serum APRIL levels only negatively correlate with hemoglobin levels and platelet counts. These correlations seem to be associated with tumor burden rather than the prognosis, because APRIL levels were not different in chemotherapy receiving patients compared to healthy controls. Since a median survival time could not be reached in the APRIL low group, short follow up time might be an explanation why the APRIL levels did not predict the time to first treatment. In conclusion, our findings let us to think APRIL levels are not a useful marker to predict prognosis in patients with CLL. Figure 1. Median APRIL levels of CLL patients and healthy controls (ng/mL) Figure 1. Median APRIL levels of CLL patients and healthy controls (ng/mL) Disclosures No relevant conflicts of interest to declare.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 109-109
Author(s):  
Hidekazu Hirano ◽  
Ken Kato ◽  
Shoko Nakamura ◽  
Yusuke Sasaki ◽  
Naoki Takahashi ◽  
...  

109 Background: Definitive chemoradiotherapy (dCRT) is one of the treatment options for stage II/III esophageal squamous cell carcinoma (ESCC). RTOG9405 demonstrated that a higher dose of radiation (64.8 Gy) offered no additional survival benefit over the standard dose (50.4 Gy). We compared the long-term outcomes of dCRT with radiation doses of 60 Gy and 50.4 Gy for ESCC. Methods: Selection criteria included thoracic ESCC, stage II/III (non T4), performance status (PS) 0-2, age 20-75 years, adequate organ function and no other active malignancy. We retrospectively analyzed patients who received dCRT as a first-line therapy between Jan. 2000 and Nov. 2011 in our hospital. Group A (n = 180) received 2 cycles of cisplatin (C) (40 mg/m2 on day 1 and 8) with fluorouracil (F) infusion (400 mg/m2/day on day 1-5 and 8-12), or 2 cycles of C (70 mg/m2 on day 1) with F infusion (700 mg/m2/day on day 1-4) repeated every 4 weeks and concurrent radiotherapy at a dose of 60 Gy. Group B (n = 62) received 2 cycles of C (75 mg/m2 on day 1) with F infusion (1000 mg/m2/day on days 1–4) repeated every 4 weeks and concurrent radiotherapy at a dose of 50.4 Gy. Overall survival (OS) and progression free survival (PFS) were estimated with the Kaplan-Meier method and compared with log-rank test. The Cox regression model was used for multivariate analysis to assess the prognostic factors for OS. Results: Characteristics of both groups were as follows (Group A: Group B): median age, 64:62; male/female, 154/26:55/7; PS 0/1/2, 81/98/1:46/16/0; T1/2/3, 39/27/114:19/9/34; N0/1, 41/139:6/56. Median follow-up period was longer than 40 months for both groups. 5-year survival rates were 44.5% for Group A and 60.0% for Group B. Median PFS and median OS were 16.5 months and 36.2 months for Group A, 41.1 months and 98.3 months for Group B. By multivariate analysis, Group B (hazard ratio [HR] 0.617: 95% confidence interval [CI]:0.400-0.951, p = 0.029), T1/2([HR] 0.383: 95% [CI]: 0.260-0.566, p < 0.001) were significant prognostic factors for OS. Conclusions: CRT with 50.4 Gy showed better long-term survival than with 60 Gy.


2017 ◽  
Vol 27 (9) ◽  
pp. 1850-1855 ◽  
Author(s):  
Takahiro Ebata ◽  
Mayu Yunokawa ◽  
Hiroshi Yoshida ◽  
Seiko Bun ◽  
Tatsunori Shimoi ◽  
...  

ObjectiveThe aim of this study was to assess the use of the pathological response to neoadjuvant chemotherapy (NAC) for predicting disease prognosis in patients with advanced ovarian cancer who received neoadjuvant dose-dense weekly paclitaxel and carboplatin (dd-TC) therapy.MethodsWe retrospectively investigated patients with advanced epithelial ovarian, tubal, or peritoneal carcinoma treated at our hospital from July 2004 to October 2014. Patients received dd-TC therapy as NAC followed by interval debulking surgery (IDS). Specimens resected during IDS were divided into 4 groups based on pathological response: grade 1, most tumor cells appeared to be viable; grade 2a, most tumor cells had disappeared, whereas the remaining tumor cells were vacuolated or degenerated; grade 2b, small numbers of viable tumor cells were observed; and grade 3, small aggregations of macrophages were seen.ResultsSixty-eight patients were enrolled. The median number of NAC cycles was 3 (range, 2–6), and 51 patients (75.0%) achieved complete resection at IDS. Regarding pathological response, 7 (10.3%) patients were classified as grade 1, 11 (16.2%) as grade 2a, 46 (67.7%) as grade 2b, and 4 (5.9%) as grade 3. In univariate and multivariate analyses, grades 2b and 3 pathological responses were significant favorable prognostic factors for progression-free survival (P = 0.028; hazard ratio, 0.48; 95% confidence interval, 0.26–0.92).ConclusionsAlthough the pathological complete response rate to NAC was low in this study, both complete and good pathological responses to NAC might be favorable prognostic factors for PFS in patients with advanced ovarian cancer who receive dd-TC.


2002 ◽  
Vol 20 (16) ◽  
pp. 3508-3521 ◽  
Author(s):  
E. Raymond ◽  
W.W. ten Bokkel Huinink ◽  
J. Taïeb ◽  
J.H. Beijnen ◽  
S. Faivre ◽  
...  

PURPOSE: The objectives were to determine the maximum-tolerated dose, the recommended dose, the dose-limiting toxicity, the pharmacokinetics, and the activity of E7070, a novel cell-cycle inhibitor. PATIENTS AND METHODS: E7070 was given as a 1-hour intravenous infusion every 3 weeks in two groups of patients with advanced solid tumors who met prespecified eligibility criteria (group A) or who met the same eligibility criteria but in addition were less heavily pretreated and had more favorable liver functions (group B). RESULTS: Forty patients (31 patients in group A and nine patients in group B) were entered. Dose escalation proceeded through eight levels (range, 50 to 1,000 mg/m2). In group A, neutropenia and thrombocytopenia were dose-limiting toxicities occurring during the first cycle in two of seven patients treated at the doses of 700 mg/m2 and two of four patients treated at 800 mg/m2. Identical dose-limiting toxicities were observed in zero of six and two of three patients from group B at doses of 800 and 1,000 mg/m2, respectively. Other toxicities included acne-like skin eruption, mucositis, conjunctivitis, nausea, fatigue, and alopecia. At doses greater than 400 mg/m2, the area under the concentration-time curve increased disproportionately to the administered dose. Tumor stabilization lasting ≥ 6 months was observed in six assessable patients. CONCLUSION: The recommended doses of E7070 in this schedule were 700 mg/m2 (group A) and 800 mg/m2 in patients who were less heavily pretreated (group B) with a moderate tumor burden. Prolonged disease stabilization observed in this study might warrant further investigation of E7070 in selected tumor types.


2013 ◽  
Vol 23 (9) ◽  
pp. 1597-1602 ◽  
Author(s):  
Laretta Grabowska-Derlatka ◽  
Pawel Derlatka ◽  
Piotr Palczewski ◽  
Anna Danska-Bidzinska ◽  
Ryszard Pacho

ObjectiveThe aim of this study was to evaluate the feasibility of multi–detector row computed tomography (MDCT) in the differentiation between borderline ovarian tumors and ovarian cancer on the basis of tumor morphology and specific features of tumor vascularity in correlation with the results at pathology.MethodsA triphasic MDCT protocol was used for the analysis of tumor vascularity. The following features were taken into account: (1) The number of vessels in papillary projections, solid-tissue component, and septa (2 vs >2), (2) serpentine and chaotic configuration of vessels, (3) presence of microaneurysms, and (4) presence of arteriovenous microfistulas. Masses with at least 3 of 4 features were considered ovarian cancer (group A) and masses with 2 features or less as borderline tumor (group B). Radiological findings were compared with results of postoperative pathology.ResultsPathologic vessels were found in all 56 patients. Thirty-two patients were included in group A and 24 in group B. The results of pathology were as follows: in group A: 31 malignant tumors, including 31 ovarian carcinomas and 1 benign cystadenoma; in group B: 22 borderline ovarian tumors, 1 benign cystadenoma, and 1 ovarian cancer.ConclusionsMorphological evaluation of tumor vascularity in MDCT seems to be an efficient method of differentiating between borderline ovarian tumors and ovarian carcinomas. Because of a small number of cases in the current study, a further research seems justified to confirm our results. The presented MDCT-angiographic criteria showed high sensitivity (97%) and specificity (96%) in differentiation of borderline ovarian tumors and ovarian cancers as compared with pathology. The presented CT-angiographic criteria of malignancy showed an excellent interobserver agreement.


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