Characteristics of hematopoiesis in primary and recurrent ovarian cancer

2021 ◽  
pp. 39-45
Author(s):  
S. V. Chulkova ◽  
A. M. Kozhonalieva ◽  
I. S. Stylidi ◽  
I. V. Poddubnaya ◽  
A. D. Palladina ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Deep Understanding ◽  
Recurrent Ovarian Cancer ◽  
The Body ◽  
High Grade ◽  
Serous Adenocarcinoma ◽  
Primary Ovarian Cancer ◽  
Metastatic Lesions ◽  
Central Organ

Introduction. An important aspect of cancer treatment today is the concept of immuno-targeted therapy, which requires a deep understanding of the characteristics of immune reactions in the body of a cancer patient. Bone marrow is the central organ of immunopoiesis, therefore, along with the study of tumor characteristics, attention is paid to the bone marrow. The study of the cellular composition of the bone marrow in some types of cancer revealed a number of features of hematopoiesis, which requires further deeper analysis.Purpose. To study the parameters of hematopoiesis in patients with primary and recurrent ovarian cancer.Materials and methods. The paper presents data from 68 patients with a verified diagnosis of primary (n = 43) and recurrent (n = 25) ovarian cancer. The study was dominated by serous adenocarcinoma of high grade. Stage I was established in 13.2 % of cases, II – in 5.9 %, III – in 60.3 %, IV – in 20.6 %. The bone marrow was harvested by puncture of the posterior iliac spine (spina iliaca posterior superior). Parameter assessment and myelogram calculation were performed by two physicians, morphologists. The content of myelokaryocytes, indicators of granulocyte, erythroid lineage, the content of lymphocytes, monocytes were analyzed, and myelogram indices were assessed. In all patients microscopy of bone marrow samples excluded metastatic lesions. Statistical data processing was performed using the SPSS Statistics v. 21 package.Results. The analysis of bone marrow samples from patients with ovarian cancer revealed differences with the norm for both primary and recurrent ovarian cancer. Most punctates were normocellular, but average myelokaryocyte count in both groups was below normal. With recurrent ovarian cancer, a reduced content of promyelocytes and metamyelocytes was noted, whereas with primary cancer, all young forms of neutrophils was below normal. An increase in segmented neutrophils without a change in the percentage of cells of the granulocytic lineage was observed in primary ovarian cancer, and in one third of the samples of bone marrow an increased number lymphocytes and monocytes were noted. With recurrent ovarian cancer lymphocytes were increased in 2/3 of samples, monocyte – in 48 %. A change in the proportion of cells of the erythroid lineage was observed in both recurrent and primary cancers: depletion of the pool of basophilic normoblasts and polychromatophils with an unchanged number of erythrokaryocytes, an increase in oxyphilic forms were noted.Conclusion. The revealed changes in hematopoiesis in ovarian cancer reflect the aggressive course of high-grade tumors, which can be considered as a result of the systemic influence of the tumor, and the obtained data can serve as the basis for a detailed immunophenotypic study of bone marrow in ovarian cancer.

scholarly journals Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1711
Author(s):  
Michelle Bilbao ◽  
Chelsea Katz ◽  
Stephanie L. Kass ◽  
Devon Smith ◽  
Krystal Hunter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
3D Culture ◽  
Extended Period ◽  
Recurrent Ovarian Cancer ◽  
Epigenetic Therapy ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cancer Spheroids

Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients’ lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture.

Poly (ADP-ribose) polymerase inhibitors in combination with anti-angiogenic agents for the treatment of advanced ovarian cancer

2021 ◽  
Author(s):  
Olivia Le Saux ◽  
Hélène Vanacker ◽  
Fatma Guermazi ◽  
Mélodie Carbonnaux ◽  
Clémence Roméo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Advanced Ovarian Cancer ◽  
Cost Effective ◽  
Preclinical Study ◽  
The Body ◽  
Synergistic Activity ◽  
High Grade ◽  
First Line ◽  
Homologous Recombination Deficiency

Homologous recombination deficiency and VEGF expression are key pathways in high-grade ovarian cancer. Recently, three randomized practice changing trials were published: the PAOLA-1, PRIMA and VELIA trials. The use of PARP inhibitors (PARPi) following chemotherapy has become standard of care in first line. Combination of PARPi with anti-angiogenic agents has demonstrated synergistic activity in preclinical study. This review summarizes the body of evidence supporting the efficacy and safety of the combination of PARPi and anti-angiogenic drugs in first-line homologous recombination deficiency high-grade ovarian cancer leading to US FDA and EMA approvals. This double maintenance is supported by: a large benefit with bevacizumab + olaparib compared with olaparib alone, a rationale for additive effect, and a good safety and cost-effective profile.

Effective weekly docetaxel for recurrent ovarian cancer: A case report

2003 ◽  
Vol 13 (5) ◽  
pp. 683-686
Author(s):  
S. Komiyama ◽  
Y. Mizusawa ◽  
M. Onouchi ◽  
K. Takehara ◽  
A. Suzuki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Salvage Chemotherapy ◽  
Stage Iiic ◽  
Serous Adenocarcinoma ◽  
Free Survival ◽  
Weekly Docetaxel ◽  
Docetaxel Treatment ◽  
Poorly Differentiated

We experienced a case of recurrent ovarian cancer that responded to weekly docetaxel. The patient had stage IIIC ovarian cancer (poorly differentiated serous adenocarcinoma). After initial remission was achieved by chemotherapy with paclitaxel and carboplatin plus cytoreductive surgery, the disease recurred and irinotecan therapy achieved temporary remission. During maintenance therapy with oral etoposide, the disease recurred again. We then tried five courses of weekly docetaxel therapy and it successfully controlled the disease. The progression-free survival time on weekly docetaxel treatment is now 7 months and the toxicity was extremely low. This patient demonstrates the effectiveness of weekly docetaxel as salvage chemotherapy for recurrent ovarian cancer.

scholarly journals Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with BRCA1/2 Mutation: A Korean Multicenter Study

2019 ◽  
Vol 8 (11) ◽  
pp. 1920 ◽  
Author(s):  
Paik ◽  
Lee ◽  
Lee ◽  
Shin ◽  
Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real World ◽  
Partial Remission ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
High Grade ◽  
Platinum Sensitive

Background: Olaparib maintenance therapy has shown efficacy and tolerability in patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). Our aim was to present real-world experience with olaparib in Korea. Method: We included HSROC patients with BRCAm treated with olaparib maintenance at four institutions in Korea between 2016 and 2018. Medical records were reviewed for clinico-pathologic characteristics, objective response, survival outcomes, and safety. Results: One hundred HSROC patients with BRCAm were included. BRCA1 mutation was present in 71 patients (71.0%), and BRCA2 mutation was present in 23 patients (23.0%). In terms of the best objective response with olaparib maintenance in 53 patients with partial remission from most recent chemotherapy, complete remission occurred in 12 (22.6%) and partial remission in four (7.5%), while 33 patients (62.3%) had stable disease. The 24 month progression-free survival was 42.4%, and 24 month overall survival was 82.1%. Grade 3 or more adverse events were as follows: anemia in 14 patients (14.0%), neutropenia in seven patients (7.0%), thrombocytopenia in two patients (2.0%), oral mucositis in one patient (1.0%), and soft tissue infection in one patient (1.0%). Conclusions: The safety and effectiveness of olaparib maintenance treatment in a real-world study were consistent with those reported in previous clinical trials.

scholarly journals Pancreatic Metastasis of High-Grade Papillary Serous Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Yusuf Gunay ◽  
Ebru Demiralay ◽  
Alp Demirag
Keyword(s):  
Ovarian Cancer ◽  
Cystic Lesion ◽  
Pancreatic Neoplasm ◽  
Pancreatic Mass ◽  
Pancreatic Tumors ◽  
Pancreatic Metastasis ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Serous Adenocarcinoma ◽  
History Of

Introduction. Reports of epithelial ovarian carcinomas metastatic to the pancreas are very rare. We herein present a metastasis of high grade papillary serous ovarian cancer to mid portion of pancreas.Case. A 42-year-old patient was admitted with a non-specified malignant cystic lesion in midportion of pancreas. She had a history of surgical treatment for papillary serous ovarian adenocarcinoma. A cystic lesion was revealed by an abdominal computerized tomography (CT) performed in her follow up . It was considered as primary mid portion of pancreatic cancer and a distal pancreatectomy was performed. The final pathology showed high-grade papillary serous adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer.Discussion. Metastatic pancreatic cancers should be considered in patients who present with a solitary pancreatic mass and had a previous non-pancreatic malignancy. Differential diagnosis of primary pancreatic neoplasm from metastatic malignancy may be very difficult. A biopsy for tissue confirmation is required to differentiate primary and secondary pancreatic tumors. Although, the value of surgical resection is poorly documented, resection may be considered in selected patients.Conclusion. Pancreatic metastasis of ovarian papillary serous adenocarcinoma has to be kept in mind when a patient with pancreatic mass has a history of ovarian malignancy.

scholarly journals Efficacy and Safety of PARP Inhibitor Combination Therapy in Recurrent Ovarian Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Ren ◽  
Leyin Zhang ◽  
Jieru Yu ◽  
Siqi Guan ◽  
Xinyang Dai ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Combination Therapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Parp Inhibitor ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
High Grade ◽  
Efficacy And Safety

ObjectivesThough it is known to all that PARP inhibitors (PARPis) are effective when used as maintenance alone for women with recurrent ovarian cancer (ROC), little is known about whether using them in combination with other drugs would contribute to a better efficacy. We performed a systematic review and meta-analysis to explore the efficacy and safety of PARPi combination therapy compared with monotherapy.Materials and MethodsWe searched for randomized controlled trials (RCTs) that offered the date we needed in PubMed, Embase, Cochrane, and major conference. Data extraction and processing were completed by three investigators to compare OS, PFS, and ORR both in intervention and in control subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. And we evaluated the within-study heterogeneity by using subgroup and sensitivity analysis.Results and ConclusionA total of three eligible RCTs covering 343 women were included. In PFS analysis, PARP inhibitor (PARPi) combination therapy can significantly improve PFS for women with ROC when compared with the controls (HR: 0.46, 95% CI: 0.35 to 0.59), especially for those with mutated BRCA (HR: 0.29, 95% CI: 0.19 to 0.45). And in OS analysis, combination therapy is not inferior to monotherapy (HR: 0.90, 95% CI: 0.50 to 1.61). As for ORR, the effectiveness of combination therapy and monotherapy was almost the same (RR: 1.04, 95% CI: 0.82 to 1.31). Additionally, combination therapy seldom causes more adverse events, both in all-grade and in high grade.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, International Prospective Register of Systematic Reviews (PROSPERO) (identifier, CRD42018109933).

Lack of p21/Waf-1 expression and lymphocyte infiltration in primary ovarian cancer correlate with the somatic HLA-A2 expression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21059-21059
Author(s):  
E. Andersson ◽  
L. Villabona ◽  
L. Kanter ◽  
Z. Gamzatova ◽  
R. Kiessling ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Group ◽  
High Risk Group ◽  
Lymphocyte Infiltration ◽  
Serous Adenocarcinoma ◽  
Primary Ovarian Cancer ◽  
Hybridization Procedure ◽  
Oligonucleotide Hybridization ◽  
Adenocarcinoma Of The Ovary ◽  
Negative Factors

21059 Background: HLA-A2 allele is highly prevalent in Scandinavia and decreases with latitude in Europe. Similarly, ovarian cancer mortality decreases with latitude in European countries. We have previously shown that HLA-A2 is associated to a severe prognosis in serous adenocarcinoma of the ovary in stage III-IV. Others have shown that lack of p21/Waf-1 and lymphocyte infiltration in this tumour is correlated to poorer prognosis as well. Here we analyse a possible linkage between these variables. Methods: Thirty eight Swedish women with epithelial ovarian cancer were analyzed for the HLA-A genotype locus by PCR/sequence-specific oligonucleotide hybridization procedure (PCR/SSOP). Tissue slides from paraffin embedded tumour material were stained with haematoxylin and antibodies anti-p21 and -p53. Results: Twenty two patients were HLA-A2 positive. Fourteen of them (37%) lacked lymphocyte infiltration wich differed significantly from HLA-A2 negative patients (n=4, 11 %) (p=0.002). All of the HLA-A2 positive patients, with serous adenocarcinoma that showed absence of tumour lymphocyte infiltration, did not express p21/waf-1 (n=7 18 %). No cases in the HLA-A2 negative group with the same parameters were identified (p=0.009). Conclusions: These observations identify a high risk group of patients by linking together the somatic expression of HLA-A2 to the lack of lymphocyte infiltration and absence of p21/Waf-1 expression at the tumour level as prognostic negative factors. The information might have a relevant impact on the patient management.. In order to obtain a stronger power the analysis will be extended to a larger group of patients. No significant financial relationships to disclose.

Recombinant Human p53 Adenovirus Injection (rAd-p53) Combined with Chemotherapy for 4 Cases of High-grade Serous Ovarian Cancer

2020 ◽  
Vol 20 (4) ◽  
pp. 313-320
Author(s):  
Hui Qu ◽  
Yu Xia ◽  
Xiuqin Li
Keyword(s):  
Ovarian Cancer ◽  
Gene Therapy ◽  
Recurrent Ovarian Cancer ◽  
Treatment Method ◽  
High Grade ◽  
Naive Patient ◽  
Treatment Naïve ◽  
Control Tumor

Background: High-grade serous ovarian carcinoma (HGSOC) is one of the most common ovarian epithelial carcinomas. It is highly invasive, easily recurs after systemic treatment, and has a poor prognosis. Despite many new chemotherapeutic drugs and trials of combinations of different regimens that have been used in treatment attempts, there has been no meaningful progress in the treatment of HGSOC. With the development of gene sequencing technology, gene therapy has become a new direction for tumors treatment. It is reported that the P53 has a very high mutation rate in HGSOC, which provides a theoretical basis for the application of gene therapy in HGSOC patients. Recombinant human p53 adenovirus injection (rAd-p53) is the world's first approved oncology gene therapy drug. Case Report: In this article, we retrospectively analyzed 4 cases of HGSOC patients treated with rAdp53. Three of them were recurrent ovarian cancer, and one was the initial treatment. The treatment method was to apply recombinant human p53 adenovirus injection (rAd-p53) to the lesions for local injection, 72 hours later, the lesions were injected with bleomycin or fluorouracil, and systemic intravenous chemotherapy was performed simultaneously. After rAd-p53 treatment, one of the three relapsed ovarian cancers achieved complete remission(CR), one achieved partial remission (PR), and one was stable disease (SD); the treatment-naive patient was operated after rAd-p53 combined with neoadjuvant chemotherapy and achieved pathological CR. Under the action of various mechanisms of P53, the subsequent tumor treatment showed the characteristics of slow tumor progression, no ascites, and local recurrence. As of the end of follow-up, the OS of 4 patients was 71-120 months. Conclusion: Through the remarkable efficacy of these 4 cases, we can see that the application of rAdp53 combined with chemotherapy can effectively control tumor lesions, prolong the survival time of patients, improve the quality of life of patients, which provide valuable experiences for rAd-p53 treatment in ovarian cancer, promote the further development and progress of gene therapy in this field.

scholarly journals The Role of Secondary Surgery in Recurrent Ovarian Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
D. Lorusso ◽  
M. Mancini ◽  
R. Di Rocco ◽  
R. Fontanelli ◽  
F. Raspagliesi
Keyword(s):  
Ovarian Cancer ◽  
Randomized Trials ◽  
Advanced Ovarian Cancer ◽  
Recurrent Ovarian Cancer ◽  
Review Of Literature ◽  
Secondary Surgery ◽  
Primary Ovarian Cancer ◽  
Literature Evidence ◽  
Major Treatment

Despite optimal treatment (complete cytoreduction and adjuvant chemotherapy), 5-year survival for advanced ovarian cancer is approximately 30% and most patients succumb to their disease. Cytoreductive surgery is accepted as a major treatment of primary ovarian cancer but its role in recurrent disease is controversial and remains a field of discussion mainly owing to missing data from prospective randomized trials. A critical review of literature evidence on secondary surgery in recurrent ovarian cancer will be described.

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