DataSheet_1_Health-related quality of life and patient-centred outcomes with COVID-19 vaccination in patients with breast cancer and gynaecological malignancies.pdf

IntroductionSafety and tolerability of COVID-19 vaccines were demonstrated by several clinical trials which led to the first FDA/EMA approvals in 2021. Because of mass immunizations, most social restrictions were waived with effects on quality of life. Therefore, our a-priori hypothesis was that COVID-19 vaccination impacted the health-related quality of life (HR-QoL) in patients with breast and gynecological cancer.MethodsFrom March 15th until August 11th, 2022, fully vaccinated patients with breast and gynecological cancer treated in the oncological outpatient clinics of the Department of Obstetrics and Gynecology, LMU University Hospital, Munich, Germany filled out a vaccine related QoL survey. Patients were asked about demographics (age, comorbidities), clinical parameters related to previous COVID-19 infections, and HR-QoL related parameters (living situation, responsibilities in everyday life). Subsequently, a questionnaire with 12 items was designed using a 5-point Likert scale (0 – strongly disagree/4 – strongly agree), covering the aspects health and therapy, social environment, participation in everyday life and overall assessment.ResultsBy August 11th, 2022, 108 out of 114 (94.7%) patients had received at least three doses of COVID-19 vaccine and six patients at least two doses. More than half of the surveyed patients were >55y (52.6%; mean: 55.1y, range 29-86y). Patients with breast cancer (n= 83) had early (59.0%) or metastatic cancer (41.0%); gynecological cancers (n=31) also included metastatic (54.8%) and non-metastatic cancer (45.2%). 83.3% of the patients stated that COVID-19 vaccination had a positive impact on their HR-QoL. Furthermore, 29 patients (25.4%) had undergone a COVID-19 infection. These patients reported self-limiting symptoms for a median duration of 5.9 days and no hospital admissions were registered.ConclusionsOur study demonstrates that vaccination against COVID-19 was positively associated with HR-QoL in patients with breast and gynecological cancer. Furthermore, vaccinated patients who underwent COVID-19 disease experienced only self-limiting symptoms.</p

Clinicopathological hallmarks and biomarkers of colorectal neuroendocrine neoplasms

<div><p>Chromogranin A (CgA) is a well-established marker for diagnosis and follow up of patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). Recently, it has been shown that plasma levels of CgA correlate with tumor load and predict survival of patients with NEN of the small bowel. It is assumed that this is as well valid for NEN of the colon and rectum, however, this is not supported by data. To evaluate this assumption, we analyzed 62 patients with NEN of the colon and rectum listed in the Marburg GEP-NEN registry for clinicopathological characteristics, expression and plasma levels of CgA. The present study demonstrates that immunohistochemical CgA and synaptophysin are good markers for histological diagnosis in patients with NEN of the colon and rectum. However, plasma CgA is a poor marker to follow-up these patients because only a minority exhibited increased levels which did not increase significantly during tumor progression. In contrast to NEN of the small bowel, there is no correlation of CgA plasma levels with tumor burden or survival. Patients with NEN of the colon and rectum displayed a relatively good prognosis resulting in a median survival of 8.5 years. However, a subset of patients affected by G3 neoplasms, exhibited a poorer prognosis with a median survival of 2.5 years. Taken together, CgA is a valuable marker for immunohistochemical diagnosis, but CgA plasma concentration is not suitable to mirror tumor burden or prognosis in patients with NEN of the colon and rectum.</p></div

Maximum levels of tumor markers tested in patients with colorectal NEN.

<p>Maximum plasma levels ever measured at our hospital for the individual GEP-NEN patients for CgA (n = 59), serotonin (n = 42), urine elimination of 5-HIAA (n = 39), CEA (n = 29) and CA19-9 (n = 21) are displayed (A). Representative evaluations of CgA, Serotonin and CA19-9 in consideration of metastatic disease are shown in Fig 3B. The red lines represent the cutoff levels for significant elevation of the individual tumor markers (CgA (50 U/l), serotonin (450 ng/ml) and CA19-9 (27U/ml)).</p

Immunohistochemistry in colorectal and intestinal NEN.

<p>Representative histological sections of well-differentiated (G1 and G2) neuroendocrine tumors and poorly differentiated colorectal NEN (A) and well-differentiated (G1) NET of the small bowel (B) are displayed after immunohistochemical staining for CgA and synaptophysin.</p

Plasma CgA levels in patients with confirmed tumor progression.

<p>Matched pairs of plasma CgA are shown before (timepoint 1) and after (timepoint 2) a confirmed tumor progression in patients with colorectal NEN (A, n = 20) and with NEN of the small bowel (B, n = 18). CT or MRI scans confirmed tumor progression according to RECIST criteria. The interval of tumor progression ranges from six to twelve months.</p

Survival rates of patients with colorectal NEN.

<p>A: A Kaplan-Meier plot displays the overall survival of 56 patients with colorectal NEN (median OS colon 4.0 years and 8.5 years for rectum). B: A Kaplan-Meier plot shows the survival analysis of three different subgroups based on grading who differ in their prognosis: The first group (30 patients, blue line, G1 tumor, Ki67: <2%, median OS not reached (n.r.)), the second group (11 patients, green line, G2 tumor, Ki67: ≤20%, median OS 4.5 years) displayed an intermediate prognosis and the third group (14 patients, red line, G3 tumor, Ki67: >20%) exhibits the worst prognosis with a median OS of 2.5 years.</p

Clinical characteristics of 62 evaluated patients with NEN of the colon and rectum.

<p>Clinical characteristics of 62 evaluated patients with NEN of the colon and rectum.</p

Epigenetic Regulation of Autophagy by the Methyltransferase G9a

Macroautophagy is an evolutionarily conserved cellular process involved in the clearance of proteins and organelles. Although the cytoplasmic machinery that orchestrates autophagy induction during starvation, hypoxia, or receptor stimulation has been widely studied, the key epigenetic events that initiate and maintain the autophagy process remain unknown. Here we show that the methyltransferase G9a coordinates the transcriptional activation of key regulators of autophagosome formation by remodeling the chromatin landscape. Pharmacological inhibition or RNA interference (RNAi)-mediated suppression of G9a induces LC3B expression and lipidation that is dependent on RNA synthesis, protein translation, and the methyltransferase activity of G9a. Under normal conditions, G9a associates with the LC3B, WIPI1, and DOR gene promoters, epigenetically repressing them. However, G9a and G9a-repressive histone marks are removed during starvation and receptor-stimulated activation of naive T cells, two physiological inducers of macroautophagy. Moreover, we show that the c-Jun N-terminal kinase (JNK) pathway is involved in the regulation of autophagy gene expression during naive-T-cell activation. Together, these findings reveal that G9a directly represses genes known to participate in the autophagic process and that inhibition of G9a-mediated epigenetic repression represents an important regulatory mechanism during autophagy