ovarian adenocarcinoma
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Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 301
Author(s):  
Khalid Zoghebi ◽  
Hamidreza Montazeri Aliabadi ◽  
Rakesh Kumar Tiwari ◽  
Keykavous Parang

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]9 containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)8WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the corresponding physical mixture of the peptide and Dox to evaluate the effectiveness of synthesized conjugate compared to the parent drug alone. [(WR)8WKβA]-Dox conjugate showed higher antiproliferative activity at 10 µM and 5 µM than Dox alone at 5 μM. The conjugate inhibited the cell viability of ovarian adenocarcinoma (SK-OV-3) by 59% and the triple-negative breast cancer cells MDA-MB-231 and MCF-7 by 71% and 77%, respectively, at a concentration of 5 μM after 72 h of incubation. In contrast, Dox inhibited the proliferation of SK-OV-3, MDA-MB-231, and MCF-7 by 35%, 63%, and 57%, respectively. Furthermore, [(WR)8WKβA]-Dox conjugate (5 µM) inhibited the cell viability of Dox-resistant cells (MES-SA/MX2) by 92%, while the viability of cells incubated with free Dox was only 15% at 5 μM. Confocal microscopy images confirmed the ability of both Dox conjugate and the physical mixture of the peptide with the drug to deliver Dox through an endocytosis-independent pathway, as the uptake was not inhibited in the presence of endocytosis inhibitors. The stability of Dox conjugate was observed at different time intervals using analytical HPLC when the conjugate was incubated with 25% human serum. Half-life (t1/2) for [(WR)8WKβA]-Dox conjugate was (∼6 h), and more than 80% of the conjugate was degraded at 12 h. The release of free Dox was assessed intracellularly using the CCRF-CEM cell line. The experiment demonstrated that approximately 100% of free Dox was released from the conjugate intracellularly within 72 h. These data confirm the ability of the cyclic cell-penetrating peptide containing tryptophan and arginine residues as an efficient tool for delivery of Dox and for overcoming resistance to it.


Morphologia ◽  
2021 ◽  
Vol 15 (1) ◽  
pp. 73-78
Author(s):  
R.A. Chyzhma ◽  
A.P. Nykolenko ◽  
A.M. Piddubnyi ◽  
R.A. Moskalenko

Background. Ovarian cancer is a very important pathology of the female reproductive system and tends to increase in incidence and mortality rates around the world. Despite the fact that ovarian cancer prevalence is lower than that of breast and cervical cancer, its mortality rate is three times higher. Aim. To analyze the incidence of ovarian cancer in the female population of Ukraine and the Sumy region in 2014–2018. Methods. Data from the National Cancer Register of Ukraine were used for this work. A statistical analysis of the incidence rates of ovarian cancer in the population of Ukraine and Sumy region was carried out. Results. The highest incidence of ovarian cancer in the Sumy region was detected in 2018 (12.5 cases per 100,000 women), and the lowest - in 2017 (10.4 cases per 100,000 women). This pathology occurs most often in women 60-79 years old. 91% of the tumors were epithelial-stromal tumors, of which 75% were serous ovarian adenocarcinomas. Ovarian cancer in most cases was diagnosed at the third stage of the disease (47% of cases), which indicates a low level of early diagnosis of this tumor. Conclusion. In the Sumy region, a high incidence rate of ovarian cancer was revealed, which exceeds the national one and has a significant age dependence. Serous ovarian adenocarcinoma is the most common type of ovarian cancer. This pathology is diagnosed mainly at the 3rd stage.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Daniela Šimčíková ◽  
Dominik Gardáš ◽  
Kateřina Hložková ◽  
Martin Hruda ◽  
Petr Žáček ◽  
...  

Abstract Background Hexokinases (HKs) are well-studied enzymes catalyzing the first step of glycolysis. However, non-canonical regulatory roles of HKs are still incompletely understood. Here, we hypothesized that HKs comprise one of the missing links between high-dose metformin and the inhibition of the respiratory chain in cancer. Methods We tested the isoenzyme-specific regulatory roles of HKs in ovarian cancer cells by examining the effects of the deletions of HK1 and HK2 in TOV-112D ovarian adenocarcinoma cells. We reverted these effects by re-introducing wild-type HK1 and HK2, and we compared the HK1 revertant with the knock-in of catalytically dead HK1 p.D656A. We subjected these cells to a battery of metabolic and proliferation assays and targeted GC×GC-MS metabolomics. Results We found that the HK1 depletion (but not the HK2 depletion) sensitized ovarian cancer cells to high-dose metformin during glucose starvation. We confirmed that this newly uncovered role of HK1 is glycolysis-independent by the introduction of the catalytically dead HK1. The expression of catalytically dead HK1 stimulated similar changes in levels of TCA intermediates, aspartate and cysteine, and in glutamate as were induced by the HK2 deletion. In contrast, HK1 deletion increased the levels of branched amino acids; this effect was completely eliminated by the expression of catalytically dead HK1. Furthermore, HK1 revertants but not HK2 revertants caused a strong increase of NADPH/NADP ratios independently on the presence of glucose or metformin. The HK1 deletion (but not HK2 deletion) suppressed the growth of xenotransplanted ovarian cancer cells and nearly abolished the tumor growth when the mice were fed the glucose-free diet. Conclusions We provided the evidence that HK1 is involved in the so far unknown glycolysis-independent HK1–metformin axis and influences metabolism even in glucose-free conditions.


2021 ◽  
pp. 151197
Author(s):  
Sandra Abdellatef ◽  
Isabelle Fakhoury ◽  
Maria Al Haddad ◽  
Leila Jaafar ◽  
Hiba Maalouf ◽  
...  

2021 ◽  
Vol 172 (2) ◽  
pp. 191-194
Author(s):  
F. V. Donenko ◽  
S. M. Sitdikova ◽  
Yu. I. Dolzhikova ◽  
Yu. S. Lebedin

2021 ◽  
pp. 1-19
Author(s):  
Varsha V. Ramoutar ◽  
Yvette J. Johnson ◽  
Laura J. Kohrt ◽  
Janice M. Bahr ◽  
Aya Iwai ◽  
...  

2021 ◽  
Vol 22 (6) ◽  
Author(s):  
Guifang Zhang ◽  
Dan Zheng ◽  
Xiaoqing Chen ◽  
Li Li ◽  
Jingrong Yu

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Cameron Boyle ◽  
Katherine Lowe ◽  
Ahmed Dhaif ◽  
Adeeb Hassan ◽  
Kawan Shalli ◽  
...  

Abstract Aim To present a rare incidental synchronous triple tumours - colonic adenocarcinoma, endometroid ovarian adenocarcinoma and benign Brenner tumour in a patient admitted with acute gallstone pancreatitis. Methods A 75-year-old female presented with epigastric pain. Blood-tests and USS abdomen confirmed gallstones and pancreatitis. She was treated conservatively. USS also showed incidental pelvic mass which was further characterised by CT and MR scans. These scans confirmed heterogeneous lobulated mass in the left adnexa. CT scan also picked-up incidental mass in transverse colon, which was confirmed as cancer by colonoscopy. She was offered therapeutic resection after discussion in Colorectal and Gynaecology MDT. Intra-operatively, transverse colonic tumour was invading into the proximal ileum. Laprascopic surgery concluded with extended right hemicolectomy, small bowel resection-anastomosis, omentectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy. Results The patient had gradual recovery without any complications. Histopathology showed T4N2 poorly differentiated adenocarcinoma of colonic mass, FIGO grade 1 stage 1c endometrioid adenocarcinoma of left ovary and benign brenner tumour of right ovary. Post-operative MDT did not offer adjuvant-therapy due to slow recovery and fraility. So far, two-years of follow-up did not show any recurrence. Conclusion This report adds to the limited literature of triple synchronous tumours, including rare Brenner accounting for 5% of benign ovarian tumours and endometrioid ovarian tumour with an incidence of 4 -7%. Multi-disciplinary approach and combined surgery can achieve a desirable outcome in such complex cases. It is crucial to identify the primary status of the tumours as it will guide the adjuvant treatment.


CHEST Journal ◽  
2021 ◽  
Vol 160 (4) ◽  
pp. A1504
Author(s):  
Emily Smallwood ◽  
Abdulmetin Dursun ◽  
Badri Giri

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