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Frontiers in Oncology 2024Ovarian cancer is a prevalent malignant tumor of the female reproductive system, often remaining concealed until it reaches an advanced stage. The standard treatment...
Ovarian cancer is a prevalent malignant tumor of the female reproductive system, often remaining concealed until it reaches an advanced stage. The standard treatment protocol includes cytoreductive surgery for ovarian cancer plus postoperative consolidation chemotherapy and maintenance therapy, although it carries a high recurrence rate. During the treatment period, chemotherapy can lead to bone marrow suppression, a condition known as Chemotherapy-Induced Myelosuppression (CIM). This suppression may necessitate dose reduction or chemotherapy treatment cycle delay. In severe cases, CIM can result in infection, fever, and potential harm to the patient's life. Here, we report a case of a female patient with ovarian malignant tumor of biochemical recurrence who treated with chemotherapy combined with Trilaciclib, following previous perioperative chemotherapy with occurrence of severe CIM. It involves an intravenous injection of Trilaciclib before chemotherapy, which significantly abates the side effects of chemotherapy, reduces the occurrence of severe CIM, improves the patients' quality of life, and decreases the economic burden of hospitalization. We hope that this retrospective analysis of the case may serve as a reference in preventing and treating severe CIM during chemotherapy in some patients with malignant tumors, ultimately benefiting more patients with tumors.
PubMed: 38764584
DOI: 10.3389/fonc.2024.1343239 -
BMJ Open Respiratory Research May 2024Targeted low-dose CT lung cancer screening reduces lung cancer mortality. England's Targeted Lung Health Check programme uses risk prediction tools to determine...
INTRODUCTION
Targeted low-dose CT lung cancer screening reduces lung cancer mortality. England's Targeted Lung Health Check programme uses risk prediction tools to determine eligibility for biennial screening among people with a smoking history aged 55-74. Some participants initially ineligible for lung cancer screening will later become eligible with increasing age and ongoing tobacco exposure. It is, therefore, important to understand how many people could qualify for reinvitation, and after how long, to inform implementation of services.
METHODS
We prospectively predicted future risk (using Prostate, Lung, Colorectal and Ovarian trial's risk model (PLCO) and Liverpool Lung Project version 2 (LLP) risk models) and time-to-eligibility of 5345 participants to estimate how many would become eligible through the course of a Lung Health Check screening programme for 55-74 years.
RESULTS
Approximately a quarter eventually become eligible, with those with the lowest baseline risks unlikely to ever become eligible. Time-to-eligibility is shorter for participants with higher baseline risk, increasing age and ongoing smoking status. At a PLCO threshold ≥1.51%, 68% of those who continue to smoke become eligible compared with 18% of those who have quit.
DISCUSSION
Predicting which participants may become eligible, and when, during a screening programme can help inform reinvitation strategies and service planning. Those with risk scores closer to the eligibility threshold, particularly people who continue to smoke, will reach eligibility in subsequent rounds while those at the lowest risk may be discharged from the programme from the outset.
Topics: Humans; Lung Neoplasms; Middle Aged; Male; Aged; Early Detection of Cancer; Female; Tomography, X-Ray Computed; Prospective Studies; England; Smoking; Risk Assessment; Eligibility Determination; Mass Screening; Risk Factors
PubMed: 38754907
DOI: 10.1136/bmjresp-2023-002193 -
Virus Research Jul 2024Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus with a wide geographic spread that can cause severe and lethal disease. No specific medical...
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus with a wide geographic spread that can cause severe and lethal disease. No specific medical countermeasures are approved to combat this illness. The CCHFV L protein contains an ovarian tumor (OTU) domain with a cysteine protease thought to modulate cellular immune responses by removing ubiquitin and ISG15 post-translational modifications from host and viral proteins. Viral deubiquitinases like CCHFV OTU are attractive drug targets, as blocking their activity may enhance cellular immune responses to infection, and potentially inhibit viral replication itself. We previously demonstrated that the engineered ubiquitin variant CC4 is a potent inhibitor of CCHFV replication in vitro. A major challenge of the therapeutic use of small protein inhibitors such as CC4 is their requirement for intracellular delivery, e.g., by viral vectors. In this study, we examined the feasibility of in vivo CC4 delivery by a replication-deficient recombinant adenovirus (Ad-CC4) in a lethal CCHFV mouse model. Since the liver is a primary target of CCHFV infection, we aimed to optimize delivery to this organ by comparing intravenous (tail vein) and intraperitoneal injection of Ad-CC4. While tail vein injection is a traditional route for adenovirus delivery, in our hands intraperitoneal injection resulted in higher and more widespread levels of adenovirus genome in tissues, including, as intended, the liver. However, despite promising in vitro results, neither route of in vivo CC4 treatment resulted in protection from a lethal CCHFV infection.
Topics: Animals; Hemorrhagic Fever Virus, Crimean-Congo; Hemorrhagic Fever, Crimean; Mice; Disease Models, Animal; Adenoviridae; Virus Replication; Viral Proteins; Genetic Vectors; Antiviral Agents; Female; Liver; Humans
PubMed: 38754786
DOI: 10.1016/j.virusres.2024.199398 -
Zhonghua Zhong Liu Za Zhi [Chinese... May 2024To analyze the effects of changes in the spectrum of deaths from malignant tumors on the life expectancies of residents of different ages, sexes, and regions (urban or...
To analyze the effects of changes in the spectrum of deaths from malignant tumors on the life expectancies of residents of different ages, sexes, and regions (urban or rural) in Tianjin from 1999 to 2019. The Abridged Life Table method and the Arriaga's decomposition method were used to calculate the effects of changes in spectrum of deaths from malignant tumors on the life expectancies of Tianjin residents of different ages, sexes, and regions. During 1999-2019, the life expectancies increased by 4.96 years and 5.69 years for males and females, respectively, in Tianjin. The decreases in the mortalities from malignant neoplasms contributed 0.12 year (3.30%) and 0.03 year (0.77%) for males and females, respectively, to the increase during 1999-2007, and 0.05 year (3.13%) and 0.12 year (6.08%) for males and females, respectively, during 2007-2019. The decreases in the mortality rates of malignant tumors contributed the most to the increase among residents in the 60-69 years group, and the decreases in mortality rates of lung, gastric, esophageal, and liver cancers had relatively larger contribution. Lung cancer had a negative effect on the life expectancies of men and rural residents, but a positive effect on those of women and urban residents. The significant increases in the mortality rates of lung, colorectal, and pancreatic cancers in the ≥85 years group had a large negative effect on the overall life expectancy. Breast and ovarian cancers contributed negatively to the life expectancy of female residents. The overall increase in the life expectancy in Tianjin from 1999 to 2019 was mainly attributed to the elderly and the decreases in the mortality rates of gastric, esophageal, and liver cancers, among other malignancies, while the increases in the mortality rates of lung, colorectal, gallbladder, pancreatic, and breast cancers were the most significant factors hindering the increase of the life expectancy in Tianjin.
Topics: Humans; Life Expectancy; Male; Female; China; Neoplasms; Middle Aged; Aged; Rural Population; Adult; Lung Neoplasms; Aged, 80 and over; Liver Neoplasms; Urban Population; Young Adult; Adolescent; Child; Esophageal Neoplasms; Infant; Child, Preschool; Stomach Neoplasms
PubMed: 38742360
DOI: 10.3760/cma.j.cn112152-20231026-00270 -
Cureus Apr 2024Chemotherapy is part and parcel of the multimodality approach to cancer treatment. Chemoports are frequently used to administer chemotherapy, preventing complications...
INTRODUCTION
Chemotherapy is part and parcel of the multimodality approach to cancer treatment. Chemoports are frequently used to administer chemotherapy, preventing complications associated with the use of peripheral lines. However, chemoports have their own set of complications and can be very debilitating at times. Accurate knowledge and correct technique can help prevent and manage these complications properly.
METHODS
We retrospectively analyzed all patients who underwent chemoport insertion for chemotherapy infusion over three years between July 2020 and June 2023. The patient's profile, type of cancer, the technique of chemoport insertion, complications related to chemoport, and its management were recorded retrospectively from patient records.
RESULTS
The total number of patients in our study was 119. The age group of patients ranged from 13 years to 76 years. Of the 119 patients, 55 had breast cancer, 23 had ovarian cancers, 29 had GI cancers including gastroesophageal junction (GEJ)/ stomach/periampullary/colorectal, and 12 had leukemias. The most common intraoperative complication was catheter tip malposition (9.2%). The most common postoperative complications were infection (7.5%), followed by drug extravasation (5.0%), thrombosis (3.3%), wound dehiscence (2.5%), and skin necrosis (0.8%) in decreasing order of frequency. Serious complications such as hemothorax, pneumothorax, air emboli, brachial plexus injury, and pericardial tamponade, commonly reported in the literature, were not seen in any of our cases.
CONCLUSION
Totally implanted venous access devices (TIVAD)/chemoports are indispensable in the management of cancer patients, especially in patients requiring long duration of infusion and prolonged treatment. Although chemoports are associated with a spectrum of complications, proper technique of implantation and use makes it a safe and reliable tool.
PubMed: 38738137
DOI: 10.7759/cureus.58052 -
Translational Cancer Research Apr 2024Microbiome and microbial dysbiosis have been proven to be involved in the carcinogenesis and treatment of gynecologic malignancies. However, there is a noticeable gap in... (Review)
Review
Microbiome and microbial dysbiosis have been proven to be involved in the carcinogenesis and treatment of gynecologic malignancies. However, there is a noticeable gap in the literature, as no comprehensive papers have covered general information, research status, and research frontiers in this field. This study addressed this gap by exploring the relationship between the gut and female reproductive tract (FRT) microbiome and gynecological cancers from a bibliometric perspective. Using VOSviewer 1.6.18, CiteSpace 6.1.R6, and HistCite Pro 2.1 software, we analyzed data retrieved from the Web of Science (WOS) Core Collection (WoSCC) database. Our dataset, consisting of 204 articles published from 2012 to 2022, revealed a consistent and upward publication trend. The United States and the United Kingdom were the primary driving forces, attributed to their prolificacy, high-quality output, and extensive cooperation. The University of Arizona Cancer Center, which is affiliated with the United States, ranked first among the top ten most prolific institutions. Frontiers in Cellular and Infection Microbiology emerged as the leading publisher. Herbst-Kralovetz MM led as the most productive author. Mitra A was the most influential author. Cervical cancer is notably associated with the microbiome, while endometrial and ovarian cancers are receiving increased attention in the last year. Intersections between the gut microbiome and estrogen are of growing importance. Current research focuses on identifying specific microbial species for etiological diagnosis, while frontiers mainly focus on the anticancer potential of microorganisms, such as regulating the effects of immune checkpoint inhibitors. In conclusion, this study sheds light on a novel and burgeoning direction of research, providing a one-stop overview of the microbiome in gynecologic malignancies. Its findings aim to help young researchers to identify research directions and future trends for ongoing investigations.
PubMed: 38737701
DOI: 10.21037/tcr-23-1769 -
MedComm May 2024Single-domain antibody-drug conjugates (sdADCs) have been proven to have deeper solid tumor penetration and intratumor accumulation capabilities due to their smaller...
Single-domain antibody-drug conjugates (sdADCs) have been proven to have deeper solid tumor penetration and intratumor accumulation capabilities due to their smaller size compared with traditional IgG format ADCs. However, one of the key challenges for improving clinical outcomes of sdADCs is their abbreviated in vivo half-life. In this study, we innovatively fused an antihuman serum albumin (αHSA) nanobody to a sdADCs targeting oncofetal antigen 5T4, conferring serum albumin binding to enhance the pharmacokinetic profiles of sdADCs. The fusion protein was conjugated with monomethyl auristatin E (MMAE) at s224c site mutation. The conjugate exhibited potent cytotoxicity against various tumor cells. Compared with the nonalbumin-binding counterparts, the conjugate exhibited a 10-fold extended half-life in wild-type mice and fivefold prolonged serum half-life in BxPC-3 xenograft tumor models as well as enhanced tumor accumulation and retention in mice. Consequently, n501-αHSA-MMAE showed potent antitumor effects, which were comparable to n501-MMAE in pancreatic cancer BxPC-3 xenograft tumor models; however, in human ovarian teratoma PA-1 xenograft tumor models, n501-αHSA-MMAE significantly improved antitumor efficacy. Moreover, the conjugate showed mitigated hepatotoxicity. In summary, our results suggested that fusion to albumin-binding moiety as a viable strategy can enhance the therapeutic potential of sdADCs through optimized pharmacokinetics.
PubMed: 38737471
DOI: 10.1002/mco2.557 -
Nutrients May 2024The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as... (Review)
Review
The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes.
Topics: Humans; Female; Vitamins; Genital Neoplasms, Female; Ovarian Neoplasms; Vitamin D; Dietary Supplements; Antineoplastic Combined Chemotherapy Protocols; Vitamin A; Antineoplastic Agents; Vitamin E
PubMed: 38732639
DOI: 10.3390/nu16091392 -
Frontiers in Endocrinology 2024Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction....
INTRODUCTION
Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients.
METHODS
This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid.
RESULTS
No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, = 0.605) and clinical pregnancy rate ( = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups.
CONCLUSION
Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.
Topics: Humans; COVID-19; Female; Pregnancy; Ovulation Induction; Adult; Retrospective Studies; Reproductive Techniques, Assisted; Pregnancy Outcome; Male; SARS-CoV-2; Pregnancy Rate; Follicular Fluid; Cytokines; Inflammation; Embryo Transfer; Treatment Outcome
PubMed: 38726341
DOI: 10.3389/fendo.2024.1353068 -
Gynecologic and Obstetric Investigation May 2024This study aimed to investigate the involvement of the cell cycle-related protein centromere protein F (CENPF) in the development of ovarian cancer (OC) and explored its...
OBJECTIVES
This study aimed to investigate the involvement of the cell cycle-related protein centromere protein F (CENPF) in the development of ovarian cancer (OC) and explored its relationship with ferroptosis.
DESIGN
The databases were analysed to identify differential expression of cell cycle-related proteins between individuals with OC and normal individuals. Immunohistochemistry and statistical analysis were conducted on ovarian tissues obtained from 40 patients with epithelial OC and 20 normal individuals. In vitro experiments were performed using SKOV3 and HEY epithelial OC cell lines.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The mRNA microarray dataset, consisting of GSE14001, GSE54388, GSE40595, and GSE14407, was downloaded from the Gene Expression Omnibus (GEO) database to investigate the genes associated with cell cycle regulation in OC cells. CENPF was selected as the subject of study through differential analysis.Assessed the expression of CENPF in both OC patients and normal ovarian tissues using immunohistochemistry. Lentivirus infection was employed to downregulate CENPF expression, and subsequent experiments including Cell Counting Kit-8 assay, cell cycle analysis, transwell assay, and wound-healing assay were conducted to investigate the effects of CENPF on proliferation, invasion, migration, and cell cycle regulation in OC cells. The reactive oxygen species (ROS) and the malondialdehyde (MDA) assays were performed to assess the involvement of CENPF in cellular redox reactions. Western blot analysis was conducted to examine the expression levels of ferroptosis-related proteins (GPX4, SLC7A11, DMT1, and protein 53 [p53]).
RESULTS
By querying and integrating cell cycle-related genes from the GEO database, in silico analyses using The Cancer Genome Atlas database combined with immunohistochemical studies, we discovered that CENPF is upregulated in OC tissues and is related to survival. Downregulation of CENPF inhibited biological function of OC cells, increased intracellular ROS and MDA levels, and downregulated the GPX4 protein and the SLC7A11/xCT protein, but upregulated the DMT1 protein and the tumour p53 expression to induce ferroptosis.
LIMITATIONS
This study did not investigate ferroptosis-related studies following CENPF overexpression, and the findings have not been validated in animal studies.
CONCLUSIONS
Our findings demonstrated that the deficiency of CENPF played a crucial anti-oncogenic role in the progression of OC through the mechanism of ferroptosis.
PubMed: 38723616
DOI: 10.1159/000539235