The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Cervical cancer – does it always require surgery?

Worldwide, cervical cancer is the second most common genital malignancy in the females. Estimated number of women affected therewith reaches 1.4 million. In Poland, cervical cancer is the fourth most common cancer, preceded by breast cancer, lung cancer and endometrial cancer, and the fifth most common cause of cancer-related mortality. Cervical cancer usually affects women aged 45-59. Current standards of treatment of cervical cancer include surgery (still the basic modality at stages 0, IA, IB and IIA), radiotherapy, chemotherapy and radiochemotherapy, which are implemented at stages IB-IVB. Surgical treatment of cervical cancer patients is classified as follows: primary treatment, treatment of coexisting genital conditions prior to planned radiochemotherapy, treatment of recurrent cervical cancer and palliative treatment. Low efficacy of radiotherapy and chemotherapy as the sole treatment modalities in cervical cancer resulted in increased interest in radiochemotherapy, i.e. a technique combining radiation with cytotoxic drugs. Randomized trials revealed an improvement of 3-years’ survival by 10-18% and the drug used most often was cisplatin administered alone or combined with a 96-hours’ infusion of fluorouracil. Cervical cancer is currently considered one of the tumors, where multimodal treatment is a therapeutic standard.W skali świata rak szyjki macicy jest drugim co do częstości występowania nowotworem narządów płciowych u kobiet. Szacuje się, że liczba kobiet chorych na raka szyjki macicy na świecie sięga 1,4 miliona. W Polsce rak szyjki macicy zajmuje czwarte miejsce – po raku sutka, płuc i endometrium – oraz piąte miejsce jako przyczyna zgonów wśród kobiet z powodu nowotworów złośliwych. Rak szyjki macicy najczęściej rozwija się u kobiet pomiędzy 45. a 59. rokiem życia. Współczesne standardy leczenia raka szyjki macicy obejmują: leczenie chirurgiczne, które wciąż jest podstawą w stopniu 0, IA, IB, IIA, radioterapię, chemioterapię oraz radiochemioterapię, które stosuje się w stopniach od IB do IVB. Leczenie chirurgiczne u chorych z rakiem szyjki macicy dzieli się na następujące typy: leczenie pierwotne, leczenie współistniejących patologii narządów płciowych przed planowaną radiochemioterapią, leczenie nawrotów raka szyjki macicy i leczenie paliatywne. Niska skuteczność radioterapii i chemioterapii stosowanych samodzielnie w raku szyjki macicy spowodowała wzrost zainteresowania radiochemioterapią, czyli metodą łączącą leczenie promieniami i lekami cytotoksycznymi. W badaniach randomizowanych stwierdzono poprawę 3-letniego przeżycia o 10-18%, a lekiem najczęściej stosowanym jest cisplatyna podawana oddzielnie lub w skojarzeniu z 96-godzinnym wlewem fluorouracylu. Rak szyjki macicy należy obecnie do nowotworów, w których leczenie skojarzone stanowi standard terapeutyczny

Progressing Vulvar Melanoma Caused by Instability in cKIT Juxtamembrane Domain: A Case Report and Review of Literature

In order to identify the molecular pathways governing melanoma and track its progression, the next-generation sequencing (NGS) approach and targeted sequencing of cancer genes were employed. The primary tumor, as well as metastatic tissue, of an 84-year-old patient diagnosed with vulvar melanoma (VM), were investigated. The primary tumor specimen showed multiple somatic mutations in TP53 gene, suggesting its major contribution to melanoma origin. The metastatic sample showed additional alterations, including other melanoma-related genes. Clinical relevancy is postulated to juxtamembrane region instability of KIT gene (c-KIT). We did not identify BRAF or NRAS alterations, which are typical for the most common melanoma pathway–MAPK cascade. However, it should be noted that this is the first report evidencing PDGFRA in melanoma, although its role in triggering VM needs to be further elucidated

The Epithelial-Mesenchymal Transition Initiated by Malignant Ascites Underlies the Transmesothelial Invasion of Ovarian Cancer Cells

The role of the epithelial-mesenchymal transition (EMT) in ovarian cancer cell progression is unquestioned. In this report, we describe that malignant ascites, fluid that accumulates in the peritoneal cavity in a large group of patients with ovarian cancer, stimulate EMT in two representative ovarian cancer cell lines (A2780, SKOV-3). In addition, we identify the ascites-derived mediators of EMT and signaling pathways initiated in the cancer cells that underlie this phenomenon. Finally, we demonstrate that EMT induced in the cancer cells in response to the malignant ascites contributes to their increased transmesothelial invasion. Altogether, our study provides new insight into the mechanistic aspects of the malignant ascites-dependent exacerbation of the intraperitoneal progression of ovarian cancer

Correction: Pakuła et al. Deciphering the Molecular Mechanism of Spontaneous Senescence in Primary Epithelial Ovarian Cancer Cells. <i>Cancers</i> 2020, <i>12</i>, 296

In the original publication [...

Correction: Paku&#322;a et al. Deciphering the Molecular Mechanism of Spontaneous Senescence in Primary Epithelial Ovarian Cancer Cells. Cancers 2020, 12, 296

In the original publication [...

Deciphering the Molecular Mechanism of Spontaneous Senescence in Primary Epithelial Ovarian Cancer Cells

Spontaneous senescence of cancer cells remains a puzzling and poorly understood phenomenon. Here we comprehensively characterize this process in primary epithelial ovarian cancer cells (pEOCs). Analysis of tumors from ovarian cancer patients showed an abundance of senescent cells in vivo. Further, serially passaged pEOCs become senescent after a few divisions. These senescent cultures display trace proliferation, high expression of senescence biomarkers (SA-β-Gal, γ-H2A.X), growth-arrest in the G1 phase, increased level of cyclins D1, D2, decreased cyclin B1, up-regulated p16, p21, and p53 proteins, eroded telomeres, reduced activity of telomerase, predominantly non-telomeric DNA damage, activated AKT, AP-1, and ERK1/2 signaling, diminished JNK, NF-κB, and STAT3 pathways, increased formation of reactive oxygen species, unchanged activity of antioxidants, increased oxidative damage to DNA and proteins, and dysfunctional mitochondria. Moreover, pEOC senescence is inducible by normal peritoneal mesothelium, fibroblasts, and malignant ascites via the paracrine activity of GRO-1, HGF, and TGF-β1. Collectively, pEOCs undergo spontaneous senescence in a mosaic, telomere-dependent and telomere-independent manner, plausibly in an oxidative stress-dependent mechanism. The process may also be activated by extracellular stimuli. The biological and clinical significance of pEOC senescence remains to be explored