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Biomedicines
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Advances in Therapeutic Strategies in Gynecological Malignant Tumors
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Advances in Therapeutic Strategies in Gynecological Malignant Tumors

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 9063

Special Issue Editor

Dr. Alberto Farolfi

E-Mail Website
Guest Editor
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
Interests: gynecologic malignancies; urogenital carcinomas; breast cancer; predictive biomarkers; DNA repair deficiency; tumor molecular profiling; immune microenvironment; cardio-oncology

Special Issue Information

Dear Colleagues,

In the last few years, new insights, novel developments, latest discoveries, and future challenges have experienced a radical change in the field of gynecologic oncology.

According to the tumor origin, gynecologic malignancies are mainly classified into ovarian cancer (epithelial, germ cell tumor, sexual-stromal tumor, and others), endometrial cancer, cervical cancer and vulvar cancer, which are recognized as global health threats for women. In recent decades, multimodal strategies consisting of surgery, radiation and chemotherapy were the main choices for these patients with gynecologic malignancies.

This research topic aims to provide updates on the newly identified molecular targets and developed therapeutic strategies for gynecological cancers, as well as discuss the recent advances in screening, diagnosis, therapies, and prognosis of gynecological cancers. We welcome submissions of articles that provide novel information in the fields encompassing, but not limited to, the identifications of cancer signaling pathways, potential therapeutic target discovery development of new targeted drugs and therapeutic strategies for gynecological cancers. The submitted articles in this Research Topic will help to highlight the current knowledge and the trend on targeted therapy of gynecological cancers.

Subtopics of interests include but are not limited to:

• Identifications of novel biomarkers for diagnosis, therapies, or prognosis for different types of gynecological cancers.
• Combinational therapeutic strategies (chemotherapy, immunotherapy, targeted agents, radiotherapy) for gynecological cancers.
• Treatment resistance strategies and mechanisms of gynecological cancers and corresponding potential therapies.
• Novel drugs for gynecological cancers.

Dr. Alberto Farolfi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • targeted therapy
  • precision medicine
  • gynecological cancers
  • ovarian cancer
  • endometrial cancer
  • cervical cancer

Published Papers (6 papers)

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Research

15 pages, 10993 KiB  
Article
Endocervical Adenocarcinoma Showing Microcystic, Elongated, and Fragmented (MELF) Pattern of Stromal Invasion: A Single-Institutional Analysis of 10 Cases with Comprehensive Clinicopathological Analyses and Ki-67 Immunostaining
by Hyunsik Bae and Hyun-Soo Kim
Biomedicines 2023, 11(11), 3026; https://doi.org/10.3390/biomedicines11113026 - 11 Nov 2023
Viewed by 663
Abstract
Microcystic, elongated, and fragmented (MELF) pattern of invasion has seldom been documented in endocervical adenocarcinoma (EAC). The aim of this study was to analyze the clinicopathological characteristics of EAC showing MELF pattern. We collected the clinicopathological information of 10 cases of EAC with [...] Read more.
Microcystic, elongated, and fragmented (MELF) pattern of invasion has seldom been documented in endocervical adenocarcinoma (EAC). The aim of this study was to analyze the clinicopathological characteristics of EAC showing MELF pattern. We collected the clinicopathological information of 10 cases of EAC with the MELF pattern and conducted polymer-based immunostaining for Ki-67 (dilution 1:200, clone MIB-1) on these cases. Ki-67 expression was assessed using the average estimation within the hotspot method. All tumors were human papillomavirus-associated EAC with Silva pattern C. All except one tumor exceeded 3 cm in size. Five tumors involved the entire thickness of the cervical stroma, and four tumors extended into the parametrium. Lymphovascular space invasion was identified in six cases. Two patients developed metastatic recurrences in the para-aortic lymph nodes and lungs, respectively. The MELF area showed significantly lower Ki-67 labelling index than that of a conventional tumor area. We confirmed our previous observation that the MELF area displayed lower proliferative activity than the conventional tumor area of EAC. We also demonstrated that patients with EAC showing MELF pattern had several adverse clinicopathological characteristics reflecting aggressive behavior. On the other hand, since the frequencies of post-operative recurrence and disease-related mortality that occurred during the follow-up period were relatively low, further investigations are warranted to clarify the prognostic value of MELF pattern in EAC patients. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies in Gynecological Malignant Tumors)
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17 pages, 16555 KiB  
Article
Combined Inhibition of Indolamine-2,3-Dioxygenase 1 and C-X-C Chemokine Receptor Type 2 Exerts Antitumor Effects in a Preclinical Model of Cervical Cancer
by Solangy Lizcano-Meneses, Rogelio Hernández-Pando, Ian García-Aguirre, José Bonilla-Delgado, Víctor Manuel Alvarado-Castro, Bulmaro Cisneros, Patricio Gariglio and Enoc Mariano Cortés-Malagón
Biomedicines 2023, 11(8), 2280; https://doi.org/10.3390/biomedicines11082280 - 16 Aug 2023
Viewed by 1211
Abstract
Cervical cancer is a public health problem diagnosed in advanced stages, and its main risk factor is persistent high-risk human papillomavirus infection. Today, it is necessary to study new treatment strategies, such as immunotherapy, that use different targets of the tumor microenvironment. In [...] Read more.
Cervical cancer is a public health problem diagnosed in advanced stages, and its main risk factor is persistent high-risk human papillomavirus infection. Today, it is necessary to study new treatment strategies, such as immunotherapy, that use different targets of the tumor microenvironment. In this study, the K14E7E2 mouse was used as a cervical cancer model to evaluate the inhibition of indolamine-2,3-dioxygenase 1 (IDO-1) and C-X-C chemokine receptor type 2 (CXCR-2) as potential anti-tumor targets. DL-1MT and SB225002 were administered for 30 days in two regimens (R1 and R2) based on combination and single therapy approaches to inhibit IDO-1 and CXCR-2, respectively. Subsequently, the reproductive tracts were resected and analyzed to determine the tumor areas, and IHCs were performed to assess proliferation, apoptosis, and CD8 cellular infiltration. Our results revealed that combined inhibition of IDO-1 and CXCR-2 significantly reduces the areas of cervical tumors (from 196.0 mm2 to 58.24 mm2 in R1 and 149.6 mm2 to 52.65 mm2 in R2), accompanied by regions of moderate dysplasia, decreased papillae, and reduced inflammation. Furthermore, the proliferation diminished, and apoptosis and intra-tumoral CD8 T cells increased. In conclusion, the combined inhibition of IDO-1 and CXCR-2 is helpful in the antitumor response against preclinical cervical cancer. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies in Gynecological Malignant Tumors)
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22 pages, 3843 KiB  
Article
Mesonephric-like Adenocarcinoma of the Uterine Corpus: Genomic and Immunohistochemical Profiling with Comprehensive Clinicopathological Analysis of 17 Consecutive Cases from a Single Institution
by Hyun-Hee Koh, Eunhyang Park and Hyun-Soo Kim
Biomedicines 2023, 11(8), 2269; https://doi.org/10.3390/biomedicines11082269 - 15 Aug 2023
Cited by 3 | Viewed by 1076
Abstract
Data on genetic and immunophenotypical characteristics of uterine mesonephric-like adenocarcinoma (MLA) remain limited. Therefore, we aimed to investigate the clinicopathological, immunohistochemical, and molecular features of uterine MLA. We performed targeted sequencing, array comparative genomic hybridization, and immunostaining in 17, 13, and 17 uterine [...] Read more.
Data on genetic and immunophenotypical characteristics of uterine mesonephric-like adenocarcinoma (MLA) remain limited. Therefore, we aimed to investigate the clinicopathological, immunohistochemical, and molecular features of uterine MLA. We performed targeted sequencing, array comparative genomic hybridization, and immunostaining in 17, 13, and 17 uterine MLA cases, respectively. Nine patients developed lung metastases. Eleven patients experienced disease recurrences. The most frequently mutated gene was Kirsten rat sarcoma viral oncogene homolog (KRAS; 13/17). Both the primary and matched metastatic tumors harbored identical KRAS (3/4) and phosphatase and tensin homolog deleted on chromosome 10 (1/4) mutations, and did not harbor any additional mutations. A total of 2 of the 17 cases harbored tumor protein 53 (TP53) frameshift insertion and deletion, respectively. Chromosomal gains were detected in 1q (13/13), 10 (13/13), 20 (10/13), 2 (9/13), and 12 (6/13). Programmed cell death-ligand 1 overexpression or mismatch repair deficiency was not observed in any of the cases. Initial serosal extension and lung metastasis independently predicted recurrence-free survival with hazard ratios of 6.30 and 7.31, respectively. Our observations consolidated the clinicopathological and molecular characteristics of uterine MLA. Both clinicians and pathologists should consider these features to make an accurate diagnosis of uterine MLA and to ensure appropriate therapeutic management of this rare entity. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies in Gynecological Malignant Tumors)
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10 pages, 1213 KiB  
Article
Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients
by Leticia Oliveira-Ferrer, Barbara Schmalfeldt, Johannes Dietl, Catharina Bartmann, Udo Schumacher and Christine Stürken
Biomedicines 2022, 10(11), 2944; https://doi.org/10.3390/biomedicines10112944 - 16 Nov 2022
Cited by 5 | Viewed by 1211
Abstract
Background: Hyaluronan (HA), a component of the extracellular matrix, is frequently increased under pathological conditions including cancer. Not only stroma cells but also cancer cells themselves synthesize HA, and the interaction of HA with its cognate receptors promotes malignant progression and metastasis. Methods: [...] Read more.
Background: Hyaluronan (HA), a component of the extracellular matrix, is frequently increased under pathological conditions including cancer. Not only stroma cells but also cancer cells themselves synthesize HA, and the interaction of HA with its cognate receptors promotes malignant progression and metastasis. Methods: In the present study, HA deposition in tissue sections was analyzed by hyaluronan-binding protein (HABP) ligand histochemistry in 17 borderline tumors and 102 primary and 20 recurrent ovarian cancer samples. The intensity and, particularly, localization of the HA deposition were recorded: for the localization, the pericellular deposition around the ovarian cancer cells was distinguished from the deposition within the stromal compartment. These histochemical data were correlated with clinical and pathological parameters. Additionally, within a reduced subgroup of ovarian cancer samples (n = 70), the RNA levels of several HA-associated genes were correlated with the HA localization and intensity. Results: Both stroma-localized and pericellular tumor-cell-associated HA deposition were observed. Cancer-cell pericellular HA deposition, irrespective of its staining intensity, was significantly associated with malignancy, and in the primary ovarian cancer cohort, it represents an independent unfavorable prognostic marker for overall survival. Furthermore, a significant association between high CD44, HAS2 and HAS3 mRNA levels and a cancer-cell pericellular HA-deposition pattern was noted. In contrast, stromal hyaluronan deposition had no impact on ovarian cancer prognosis. Conclusions: In conclusion, the site of HA deposition is of prognostic value, but the amount deposited is not. The significant association of only peritumoral cancer-cell HA deposition with high CD44 mRNA expression levels suggests a pivotal role of the CD44–HA signaling axis for malignant progression in ovarian cancer. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies in Gynecological Malignant Tumors)
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16 pages, 1655 KiB  
Article
Tumor-Specific Imaging with Angiostamp800 or Bevacizumab-IRDye 800CW Improves Fluorescence-Guided Surgery over Indocyanine Green in Peritoneal Carcinomatosis
by Véronique Josserand, Claire Bernard, Thierry Michy, Mélanie Guidetti, Julien Vollaire, Jean-Luc Coll and Amandine Hurbin
Biomedicines 2022, 10(5), 1059; https://doi.org/10.3390/biomedicines10051059 - 03 May 2022
Cited by 3 | Viewed by 1803
Abstract
Complete surgical removal of lesions improves survival of peritoneal carcinomatosis and can be enhanced by intraoperative near-infrared fluorescence imaging. Indocyanine green (ICG) is the only near-infrared fluorescent dye approved for clinical use, but it lacks specificity for tumor cells, highlighting the need for [...] Read more.
Complete surgical removal of lesions improves survival of peritoneal carcinomatosis and can be enhanced by intraoperative near-infrared fluorescence imaging. Indocyanine green (ICG) is the only near-infrared fluorescent dye approved for clinical use, but it lacks specificity for tumor cells, highlighting the need for tumor-selective targeting agents. We compared the tumor-specific near-infrared fluorescent probes Bevacizumab-IRDye 800CW and Angiostamp800, which target tumor angiogenesis and cancer cells, to ICG for fluorescence-guided surgery in peritoneal carcinomatosis of ovarian origin. The probes were administered to mice with orthotopic peritoneal carcinomatosis prior to conventional and fluorescence-guided surgery. The influence of neoadjuvant chemotherapy was also assessed. Conventional surgery removed 88.0 ± 1.2% of the total tumor load in mice. Fluorescence-guided surgery allowed the resection of additional nodules, enhancing the total tumor burden resection by 9.8 ± 0.7%, 8.5 ± 0.8%, and 3.9 ± 1.2% with Angiostamp800, Bevacizumab-IRDye 800CW and ICG, respectively. Interestingly, among the resected nodules, 15% were false-positive with ICG, compared to only 1.4% with Angiostamp800 and 3.5% with Bevacizumab-IRDye 800CW. Furthermore, conventional surgery removed only 69.0 ± 3.9% of the total tumor burden after neoadjuvant chemotherapy. Fluorescence-guided surgery with Angiostamp800 and Bevacizumab-IRDye 800CW increased the total tumor burden resection to 88.7 ± 4.3%, whereas ICG did not improve surgery at all. Bevacizumab-IRDye 800CW and Angiostamp800 better detect ovarian tumors and metastases than the clinically used fluorescent tracer ICG, and can help surgeons completely remove tumors, especially after surgery neoadjuvant chemotherapy. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies in Gynecological Malignant Tumors)
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16 pages, 2984 KiB  
Article
HDAC9 Contributes to Serous Ovarian Cancer Progression through Regulating Epithelial–Mesenchymal Transition
by Long Xu, Jian Wang, Buhan Liu, Jiaying Fu, Yuanxin Zhao, Sihang Yu, Luyan Shen, Xiaoyu Yan and Jing Su
Biomedicines 2022, 10(2), 374; https://doi.org/10.3390/biomedicines10020374 - 03 Feb 2022
Cited by 9 | Viewed by 2074
Abstract
Epithelial ovarian cancer has the highest mortality rate of all gynecological malignant tumors. Metastasis is the main cause of poor prognosis in patients with ovarian cancer. Epigenetic and protein post-translational modifications play important roles in tumor metastasis. As a member of class IIa [...] Read more.
Epithelial ovarian cancer has the highest mortality rate of all gynecological malignant tumors. Metastasis is the main cause of poor prognosis in patients with ovarian cancer. Epigenetic and protein post-translational modifications play important roles in tumor metastasis. As a member of class IIa histone deacetylases, histone deacetylase 9 (HDAC9) is involved in many biological processes by deacetylating histone and nonhistone proteins. However, its roles in ovarian cancer remain unclear. In this study, we found that patients with serous ovarian cancer with high expression of HDAC9 had poor prognoses. On the contrary, patients with non-serous ovarian cancer with high expression of HDAC9 had higher survival rates. In serous ovarian cancer, overexpressed HDAC9 may promote cell migration through the forkhead box protein O1 (FOXO1)/transforming growth factor-beta (TGF-β) axis. In non-serous ovarian cancer, overexpressed HDAC9 exerts antitumor effects that might be caused by the suppression of β-catenin signaling. Therefore, HDAC9 may be a potential target for individualized treatment of patients with different histological subtypes of ovarian cancer. Full article
(This article belongs to the Special Issue Advances in Therapeutic Strategies in Gynecological Malignant Tumors)
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