Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures.

The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020.

Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Nummer 032/034-OL, April 2018) - Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer.

The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy.

Recurrent Mastitis after Core Needle Biopsy: Case Report of an Unusual Complication after Core Needle Biopsy of a Phyllodes Tumor.

BACKGROUND: In the routine work-up of suspect breast lesions, ultrasound-controlled core needle biopsy (CNB) is the most common tool to acquire tissue for histopathologic analysis in a safe, quick and convenient way. Complications are generally rare. The most common complications are hematoma and infection, each with less than 1 in 1000 cases.

Human adenovirus replication in immunocompetent Syrian hamsters can be attenuated with chlorpromazine or cidofovir.

Background: Adenoviruses can cause severe toxicity in children and in immunocompromised adults, and therefore a means to abrogate replication would be useful. With regard to cancer treatment, replication competent oncolytic adenoviruses have been safe in humans, although their efficacy has been variable. Therefore, more effective agents are now entering clinical testing and, consequently, replication-associated side effects remain a concern.

Serotype chimeric and fiber-mutated adenovirus Ad5/19p-HIT for targeting renal cancer and untargeting the liver.

Despite some advances, patients with advanced renal cell carcinoma (RCC) cannot usually be cured. Alteration of the natural tropism of adenoviruses may permit more specific gene transfer to target tissues. The aim of this study was to use novel targeting moieties for adenoviral gene therapy of RCC.

An unusual case of advanced bilateral male breast cancer.

Background: Breast cancer in men is an uncommon disease. Little is known about its etiology, clinical behavior, treatment, and outcome. Retrospective data indicate that stage- and age-matched male and female breast cancer is similar in presentation.

Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.

Clinical trials have confirmed the safety of selectively oncolytic adenoviruses for treatment of advanced cancers. However, increasingly effective viruses could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. We analyzed viruses containing the cyclooxygenase-2 (Cox-2) or vascular endothelial growth factor (VEGF) promoter for controlling replication.

Tissue-specific promoters active in CD44+CD24-/low breast cancer cells.

It has been proposed that human tumors contain stem cells that have a central role in tumor initiation and posttreatment relapse. Putative breast cancer stem cells may reside in the CD44(+)CD24(-/low) population. Oncolytic adenoviruses are attractive for killing of these cells because they enter through infection and are therefore not susceptible to active and passive mechanisms that render stem cells resistant to many drugs.

Triple-targeted oncolytic adenoviruses featuring the cox2 promoter, E1A transcomplementation, and serotype chimerism for enhanced selectivity for ovarian cancer cells.

Conditionally replicating adenoviruses (CRAd's) feature selective replication in and killing of tumor cells. Initial clinical studies with relatively attenuated early generation agents have resulted in promising safety and efficacy data. Nevertheless, increased specificity may be advantageous for an emerging generation of infectivity-enhanced CRAd's.

A fiber-modified, secretory leukoprotease inhibitor promoter-based conditionally replicating adenovirus for treatment of ovarian cancer.

Purpose: The use of conditionally replicating adenoviruses (CRAD) is dependent on molecular differences between tumor cells and nontumor cells. Transcriptional targeting of CRAD replication via tumor-specific promoters is an effective way to control replication regulation. Genetic fiber pseudotyping is an approach for circumventing low expression of the primary adenovirus serotype 5 (Ad5) receptor by using the distinct adenovirus serotype 3 (Ad3) receptor for entry into and subsequent killing of ovarian cancer cells.

Inter-patient variation in efficacy of five oncolytic adenovirus candidates for ovarian cancer therapy.

Background: Gene therapy offers a new strategy for cancer treatment. Adenoviruses represent the most widely used gene therapy vector and feature an excellent safety record. Conditionally replicative adenoviruses (CRAds) effect solid tumor penetration and tumor selective oncolysis and consequently offer potential efficacy for metastatic disease treatment.

Evaluation of tissue-specific promoters in carcinomas of the cervix uteri.

Background: Gene therapy is a novel approach for treatment of patients with advanced, recurrent, or metastatic cervical cancer. One effective way to direct transgene expression to specific tissues or tumors is the use of tissue-specific-promoters (TSPs). In the context of adenovirus (Ad)-mediated cancer gene therapy it is rational to choose a TSP which is highly expressed in the tumor but has potentially low activity in non-tumor cells, especially the liver.

Evaluation of a selectively oncolytic adenovirus for local and systemic treatment of cervical cancer.

Treatment options for disseminated cervical cancer remain inadequate. Here, we investigated a strategy featuring Ad5-Delta 24 RGD, an oncolytic adenovirus replication-competent selectively in cells defective in the Rb-p16 pathway, such as most cervical cancer cells. The viral fiber contains an alpha(v)beta(3) and alpha(v)beta(5) integrin-binding RGD-4C motif, allowing coxsackie-adenovirus receptor-independent infection.

Enhanced therapeutic efficacy for ovarian cancer with a serotype 3 receptor-targeted oncolytic adenovirus.

Oncolytic viruses that are replication competent in tumor but not in normal cells represent a novel approach for treating neoplastic diseases. However, the oncolytic potency of replicating agents is determined directly by their capability of infecting target cells. Most adenoviruses used for gene therapy or virotherapy have been based on serotype 5 (Ad5).

Replication of an integrin targeted conditionally replicating adenovirus on primary ovarian cancer spheroids.

Replication competent viruses hold promise for treatment of advanced cancers resistant to available therapeutic modalities. Although preliminary clinical results have substantiated their efficacy, preclinical development of these novel approaches is limited by assay substrates. The evaluation of candidate agents could be confounded by differences between primary tumor cells and tumor cell lines, as discordance in the levels of surface receptors relevant for viral entry has been reported.

A canine conditionally replicating adenovirus for evaluating oncolytic virotherapy in a syngeneic animal model.

Oncolytic adenoviruses, which selectively replicate in and subsequently kill cancer cells, have emerged as a promising approach for treatment of tumors resistant to other modalities. Although preclinical results have been exciting, single-agent clinical efficacy has been less impressive heretofore. The immunogenicity of adenoviruses, and consequent premature abrogation of replication, may have been a partial reason.

Adenoviral gene therapy for cancer: from vectors to targeted and replication competent agents (review).

Gene therapy is an exciting novel approach for treating cancers resistant to currently available modalities. Treatment approaches are based on taking advantage of molecular differences between normal and tumor cells. Various strategies are currently in clinical development, with some promising early results reported with mutation compensation, molecular chemotherapy and replication competent viruses.

Gene transfer to ovarian cancer versus normal tissues with fiber-modified adenoviruses.

Adenovirus serotype 5 (Ad5) displays unparalleled gene transfer efficacy to cells with high coxsackie-adenovirus receptor (CAR) expression. Unfortunately, cells isolated from clinical human cancers, both ovarian and other types, express highly variable and often low levels of CAR. Fortunately, native Ad5 tropism can be modified to circumvent CAR deficiency and to enhance infectivity.

The flt-1 promoter for transcriptional targeting of teratocarcinoma.

Flt-1, a receptor for vascular endothelial growth factor, is known to display dysregulated expression in both tumor vasculature and tumor cells per se, suggesting that the flt-1 promoter might be a useful candidate to achieve tumor-specific transgene expression. In addition, adenoviral vectors containing transgenes under the control of the flt-1 promoter achieve very low levels of expression in the normal liver, the major organ responsible for blood clearance of adenoviruses and inadvertent transgene-related toxicity. Thus, we assessed the ability of adenoviral vectors containing the flt-1 promoter to achieve transgene expression in a range of gynecological and breast tumor lines.

Treatment of ovarian cancer with a tropism modified oncolytic adenovirus.

Ad5-Delta 24RGD is an adenovirus that is selectively replication competent in cells defective in the Rb/p16 pathway, such as ovarian cancer cells. The fiber of Ad5-Delta 24RGD contains an integrin binding RGD-4C motif, allowing Coxsackie adenovirus receptor-independent infection of cancer cells. Oncolysis of cell lines was similar to that of a wild-type control, and replication in primary tumor material was shown using a novel three-dimensional spheroid model.