Publications by authors named "Lukas Rob"

The incidence of cancer during pregnancy is steadily rising because of the postponement of plans for childbearing. One of the most common cancers diagnosed during pregnancy is cervical cancer. Diagnosis of most cases usually occurs in the early stages, but there are still cases of tumors staged IB2 and higher.

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Background: High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of epithelial ovarian carcinoma. It is primarily diagnosed at stage III or IV when the 5-year survival rate ranges between 20% and 40%. Here, we aimed to validate the hypothesis, based on HGSOC cell lines, that proposed the existence of two distinct groups of HGSOC cells with high and low oxidative phosphorylation (OXPHOS) metabolism, respectively, which are associated with their responses to glucose and glutamine withdrawal.

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Purpose: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICIs) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication.

Experimental Design: We harnessed a variety of transcriptomic, spatial and functional assays to characterize the differential impact of neo-adjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to NACT-naïve HGSOC samples from 5 independent patient cohorts.

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Impaired telomere length (TL) maintenance in ovarian tissue may play a pivotal role in the onset of epithelial ovarian cancer (OvC). TL in either target or surrogate tissue (blood) is currently being investigated for use as a predictor in anti-OvC therapy or as a biomarker of the disease progression, respectively. There is currently an urgent need for an appropriate approach to chemotherapy response prediction.

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Article Synopsis
  • Chronic endometritis is a significant, often undiagnosed cause of infertility, especially affecting in vitro fertilization (IVF) outcomes due to intrauterine inflammation.
  • The condition is associated with changes in the endometrial microbiome and characterized by mild or absent symptoms, making diagnosis challenging, typically requiring hysteroscopy and histopathological examinations.
  • Empirical antibiotic therapy has been found to increase pregnancy and live birth rates in women with confirmed chronic endometritis, highlighting the need for improved diagnostic criteria and awareness of the condition's reproductive implications.*
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  • - Tubal abortion refers to the expulsion of a fetus into the abdominal cavity from a fallopian tube, which can be either complete or partial, and is a type of ectopic pregnancy that poses challenges in accurately determining its incidence.
  • - Accurate diagnosis of tubal abortions is essential for tailored treatment, typically involving ultrasound imaging, measuring b-hCG levels, and visual confirmation during surgery.
  • - A case study of a 30-year-old woman with suspected ectopic pregnancy revealed a tubal abortion via laparoscopic surgery, allowing for a conservative treatment that preserved her fallopian tubes and potential fertility.
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Aim: To review the changes in the new version of the FIGO 2023 staging system for endometrial cancer.

Methods And Results: The new FIGO 2023 endometrial cancer staging system provides key updates for the diagnosis and treatment of endometrial cancer. An important step in diagnosis is molecular classification, which allows more accurate risk stratification for recurrence and the identification of targeted therapies.

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  • The study examined CT/MRI scans of 127 subjects (63 with cervical cancer and 64 with endometrial cancer) to compare rates of radiation-related fractures following different treatments.
  • Despite differences in treatment doses and patient characteristics like age and BMI, the fracture rates were similar: 28.6% for cervical cancer patients and 26.6% for endometrial cancer patients.
  • Lower bone density was a significant factor, as older cervical cancer patients had lower bone densities, and while endometrial cancer patients showed no age difference, they also had lower bone densities and BMIs, with overall fracture risk linked mainly to osteoporosis rather than BMI.
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Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8 effector T (T) cells and TIM3PD1, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8 T cells.

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High-grade serous ovarian carcinoma (HGSC) is the most common subtype of ovarian cancer and is among the most fatal gynecological malignancies worldwide, due to late diagnosis at advanced stages and frequent therapy resistance. In 47 HGSC patients, we assessed somatic and germline genetic variability of a custom panel of 144 known or suspected HGSC-related genes by high-coverage targeted DNA sequencing to identify the genetic determinants associated with resistance to platinum-based therapy. In the germline, the most mutated genes were DNAH14 (17%), RAD51B (17%), CFTR (13%), BRCA1 (11%), and RAD51 (11%).

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Objective: The aim of this study was to determine how often changes the stage of the tumour in definitive histology against preoperative clinical stage in patient cohort with diagnosed endometrial cancer.

Methods: We evaluated prospectively a cohort of 166 patients with endometrial cancer. They all underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node biopsy.

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The profile of the antitumor immune response is an important factor determining patient clinical outcome. However, the influence of the tissue contexture on the composition of the tumor microenvironments of virally induced tumors is not clearly understood. Therefore, we analyzed the immune landscape of two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and squamous cell carcinoma of uterine cervix (CESC).

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Introduction: Chemotherapy during pregnancy can increase the risk of fetal anemia. Severe fetal anemia can lead to the development of hydrops fetalis and potentially fetal demise. Hence, it is imperative to implement consistent monitoring methods in the context of chemotherapy treatment.

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Objective: A review of current knowledge on the efficacy of human papillomavirus (HPV) vaccination in preventing recurrent severe cervical lesions after excisional surgical treatment.

Methods And Results: HPV infection is necessary for the development of most cervical precancerous lesions and cervical cancers. Currently, three prophylactic vaccines against HPV infection are available on the market: bivalent Cervarix, quadrivalent Gardasil (formerly Silgard) and nonavalent Gardasil9.

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Introduction: The standard procedure in cervical cancer is radical hysterectomy and pelvic lymphadenectomy (PLND). Because of the increasing age of women bearing children, fertility has become a major challenge. We present pregnancy results after less radical fertility-sparing surgery in women with IA1, LVSI positive, IA2 and IB1 (<2 cm, infiltration less than half of the cervical stroma).

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Article Synopsis
  • * Results showed that younger women (under 49) made up 26% of cases, with 12.3% recurrence in cases with positive margins compared to lower rates in those with healthier margins (1-3mm).
  • * The conclusion emphasized that maintaining a minimal healthy margin (1-3mm) reduces recurrence risk while also providing a good cosmetic outcome and preserving women's psychosexual functions, highlighting the need for long-term follow-up.
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Epithelial ovarian carcinoma (EOC) is known for high mortality due to diagnosis at advanced stages and frequent therapy resistance. Previous findings suggested that the DNA repair system is involved in the therapeutic response of cancer patients and DNA repair genes are promising targets for novel therapies. This study aimed to address complex inter-relations among gene expression levels, methylation profiles, and somatic mutations in DNA repair genes and EOC prognosis and therapy resistance status.

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Epithelial ovarian carcinoma (EOC) is highly fatal because of the risk of resistance to therapy and recurrence. We performed whole-exome sequencing of blood and tumor tissue pairs of 50 patients with surgically resected EOC. Compared with sensitive patients, platinum-resistant patients had a significantly higher somatic mutational rate in <i>TP53</i> and lower in several genes from the Hippo pathway.

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Dendritic cells (DCs) have received considerable attention as potential targets for the development of novel cancer immunotherapies. However, the clinical efficacy of DC-based vaccines remains suboptimal, largely reflecting local and systemic immunosuppression at baseline. An autologous DC-based vaccine (DCVAC) has recently been shown to improve progression-free survival and overall survival in randomized clinical trials enrolling patients with lung cancer (SLU01, NCT02470468) or ovarian carcinoma (SOV01, NCT02107937), but not metastatic castration-resistant prostate cancer (SP005, NCT02111577), despite a good safety profile across all cohorts.

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Vaccination is a widely discussed topic during pregnancy and breastfeeding. Due to newly emerging covid-19 variants, vaccination has become more and more important. These new variants pose a risk for the development of maternal and neonatal complications.

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We report a case of a 49-year-old female with desmoplastic small round cell tumor of the uterus (DSRCT). Histologically, in some areas the tumor showed typical features with ample desmoplastic stroma, while in other areas the tumor cells diffusely infiltrated myometrium with only focal desmoplastic reaction. Immunohistochemically, the tumor cells showed diffuse positivity for desmin, CD56, CD57, EMA and cyclin D1.

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Purpose: The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937).

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The main problem precluding successful therapy with conventional taxanes is de novo or acquired resistance to taxanes. Therefore, novel experimental taxane derivatives (Stony Brook taxanes; SB-Ts) are synthesized and tested as potential drugs against resistant solid tumors. Recently, we reported alterations in , , and gene expression in a breast cancer cell line resistant to paclitaxel.

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Background: Most patients with epithelial ovarian cancer (EOC) relapse despite primary debulking surgery and chemotherapy (CT). Autologous dendritic cell immunotherapy (DCVAC) can present tumor antigens to elicit a durable immune response. We hypothesized that adding parallel or sequential DCVAC to CT stimulates antitumor immunity and improves clinical outcomes in patients with EOC.

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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.

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