Aldona Woźniak

Frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT in laryngeal squamous cell carcinomas and adjacent normal mucosa

Laryngeal cancers are the most frequent cancers of the head and neck region. While recent observations indicate the occurrence of an epigenetic field defect in head and neck cancer patients, a detailed exploration of the characteristic changes in the DNA methylation profile in laryngeal cancer patients was lacking. The aim of this study was to assess the methylation frequency of seven genes in a group of patients with primary laryngeal squamous cell carcinoma. Along tumor sections, matching samples of normal mucosa from epiglottis and trachea were analyzed. Gene methylation was assessed using the methylation-specific polymerase chain reaction. We found frequent gene hypermethylation in both the tumor and normal mucosa samples. The methylation of MGMT in tumor cells was associated with lymph node involvement. We report that laryngeal squamous cell carcinomas are characterized by frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT. Moreover, evidence is shown for the occurrence of a large epigenetically changed field of epithelial cells in laryngeal cancer patients. Our findings indicate the high prevalence of epigenetic abnormalities in laryngeal tumors.

Peritoneal mesothelium promotes the progression of ovarian cancer cells in vitro and in a mice xenograft model in vivo

The role of mesothelial cells in the intraperitoneal spread of ovarian cancer is still elusive. In particular, it is unclear whether these cells constitute a passive barrier preventing cancer cell progression or perhaps act as an active promoter of this process. In this report we show that omental human peritoneal mesothelial cells (HPMCs) stimulate adhesion and proliferation of ovarian cancer cells (A2780, OVCAR-3, SKOV-3). The latter was associated with the paracrine activity of GRO-1, IL-6, and IL-8 released to the environment by HPMCs. Furthermore, the growth dynamics of ovarian cancer xenografts produced in response to i.p. injection of ovarian cancer cells together with HPMCs was remarkably greater than for implantation of cancer cells alone. A layer of peritoneal mesothelium was consistently present in close proximity to the tumor mass in every xenograft model. In conclusion, our results indicate that HPMCs play a supporting role in the intraperitoneal invasiveness of ovarian malignancy, whose effect may be attributed to their ability to stimulate adhesion and proliferation of cancer cells.

Colorectal cancer-promoting activity of the senescent peritoneal mesothelium

Gastrointestinal cancers metastasize into the peritoneal cavity in a process controlled by peritoneal mesothelial cells (HPMCs). In this paper we examined if senescent HPMCs can intensify the progression of colorectal (SW480) and pancreatic (PSN-1) cancers in vitro and in vivo. Experiments showed that senescent HPMCs stimulate proliferation, migration and invasion of SW480 cells, and migration of PSN-1 cells. When SW480 cells were injected i.p. with senescent HPMCs, the dynamics of tumor formation and vascularization were increased. When xenografts were generated using PSN-1 cells, senescent HPMCs failed to favor their growth. SW480 cells subjected to senescent HPMCs displayed up-regulated expression of transcripts for various pro-cancerogenic agents as well as increased secretion of their products. Moreover, they underwent an epithelial-mesenchymal transition in the Smad 2/3-Snail1-related pathway. The search for mediators of senescent HPMC activity showed that increased SW480 cell proliferation was stimulated by IL-6, migration by CXCL8 and CCL2, invasion by IL-6, MMP-3 and uPA, and epithelial-mesenchymal transition by TGF-β1. Secretion of these agents by senescent HPMCs was increased in an NF-κB- and p38 MAPK-dependent mechanism. Collectively, our findings indicate that in the peritoneum senescent HPMCs may create a metastatic niche in which critical aspects of cancer progression become intensified.

Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian cancer cells in vitro and in a mouse xenograft model in vivo

It is believed that senescent cells contribute to the progression of primary and metastatic tumors, however, the exact mechanisms of this activity remain elusive. In this report we show that senescent human peritoneal mesothelial cells (HPMCs) alter the secretory profile of ovarian cancer cells (A2780, OVCAR-3, SKOV-3) by increasing the release of four angiogenic agents: CXCL1, CXCL8, HGF, and VEGF. Proliferation and migration of endothelial cells subjected to conditioned medium generated by: cancer cells modified by senescent HPMCs; cancer cells co-cultured with senescent HPMCs; and by early-passage HPMCs from aged donors, were markedly intensified. The same was the case for the vascularization, size and number of tumors that developed in the mouse peritoneum upon injection of ovarian cancer cells with senescent HPMCs. When the identified pro-angiogenic proteins were neutralized in conditioned medium from the cancer cells, both aspects of endothelial cell behavior intensified in vitro in response to senescent HPMCs were markedly reduced. The search for mediators of senescent HPMC activity using specific neutralizing antibodies and recombinant exogenous proteins showed that the intensified angiogenic potential of cancer cells was elicited by IL-6 and TGF-β1. At the transcriptional level, increased proliferation and migration of endothelial cells exposed to cancer cells modified by senescent HPMCs was regulated by HIF-1α, NF-κB/p50 and AP-1/c-Jun. Collectively, our findings indicate that senescent HPMCs may promote the progression of ovarian cancer cells by reprogramming their secretory phenotype towards increased production of pro-angiogenic agents and subsequent increase in the angiogenic capabilities of the vascular endothelium.

Senescent peritoneal mesothelium creates a niche for ovarian cancer metastases

Although both incidence and aggressiveness of ovarian malignancy rise with age, the exact reason for this tendency, in particular the contribution of senescent cells, remains elusive. In this project we found that the patient’s age determines the frequency of intraperitoneal metastases of ovarian cancer. Moreover, we documented that senescent human peritoneal mesothelial cells (HPMCs) stimulate proliferation, migration and invasion of ovarian cancer cells in vitro, and that this effect is related to both the activity of soluble agents released to the environment by these cells and direct cell-cell contact. The panel of mediators of the pro-cancerous activity of senescent HPMCs appeared to be cancer cell line-specific. The growth of tumors in a mouse peritoneal cavity was intensified when the cancer cells were co-injected together with senescent HPMCs. This effect was reversible when the senescence of HPMCs was slowed down by the neutralization of p38 MAPK. The analysis of lesions excised from the peritoneum of patients with ovarian cancer showed the abundance of senescent HPMCs in close proximity to the cancerous tissue. Collectively, our findings indicate that senescent HPMCs which accumulate in the peritoneum in vivo may create a metastatic niche facilitating intraperitoneal expansion of ovarian malignancy.

Oxidative stress contributes to hepatocyte growth factor-dependent pro-senescence activity of ovarian cancer cells

Abstract The cancer‐promoting activity of senescent peritoneal mesothelial cells (HPMCs) has already been well evidenced both in vitro and in vivo. Here we sought to determine if ovarian cancer cells may activate senescence in HPMCs. The study showed that conditioned medium (CM) from ovarian cancer cells (OVCAR‐3, SKOV‐3, A2780) inhibited growth and promoted the development of senescence phenotype (increased SA‐&bgr;‐Gal, &ggr;‐H2A.X, 53BP1, and decreased Cx43) in HPMCs. An analysis of tumors isolated from the peritoneum of patients with ovarian cancer revealed an abundance of senescent HPMCs in proximity to cancerous tissue. The presence of senescent HPMCs was incidental when fragments of peritoneum free from cancer were evaluated. An analysis of the cells’ secretome followed by intervention studies with exogenous proteins and neutralizing antibodies revealed hepatocyte growth factor (HGF) as the mediator of the pro‐senescence impact of the cancer cells. The activity of cancerous CM and HGF was associated with an induction of mitochondrial oxidative stress. Signaling pathways involved in the senescence of HPMCs elicited by the cancer‐derived CM and HGF included p38 MAPK, AKT and NF‐&kgr;B. HPMCs that senesced prematurely in response to the cancer‐derived CM promoted adhesion of ovarian cancer cells, however this effect was effectively prevented by the cell protection against oxidative stress. Collectively, our findings indicate that ovarian cancer cells can elicit HGF‐dependent senescence in HPMCs, which may contribute to the formation of a metastatic niche for these cells within the peritoneal cavity. Graphical abstract Figure. No caption available. HighlightsConditioned medium (CM) from ovarian cancer cells induces senescence in HPMCs.Hepatocyte growth factor (HGF) mediates the pro‐senescence activity of cancerous CM.Activity of cancerous CM/HGF is associated with the induction of oxidative stress.Signaling pathways underlying activity of CM/HGF include AKT, p38 MAPK and NF‐&kgr;B.HPMCs senesced in response to cancerous CM/HGF promote ovarian cancer cell adhesion.

Comparison between high‐frequency ultrasonography (Dermascan C, version 3) and histopathology in atopic dermatitis

The main purpose of this study was the exact comparison of B‐scan images obtained from 16 patients suffering from AD with histological.

Medullary thyroid carcinoma — PET/CT imaging with 68Ga-labelled gastrin and somatostatin analogues

CASE PRESENTATION a 75-year-old man with a 10-year history of nodular goitre was referred for clinical evaluation. The ultrasound scan revealed enlarged thyroid right lobe almost fully filled with a heterogeneous nodule with numerous calcifications. Fine-needle aspiration biopsy suggested medullary thyroid carcinoma (MTC). Before the surgery the patient was referred to the nuclear medicine department and somatostatin receptor imaging (SRS; 68Ga-DOTATATE) with PET/CT was performed. The scan demonstrated an increased uptake within the right thyroid mass. Subsequent PET/CT with 68Ga-gastrin analogue (MG48) revealed the same indications as the SRS: an increased alveolar uptake in the right thyroid mass without the signs of lymph node metastases. The patient underwent total thyroidectomy and central lymph nodes dissection. Histopathology examination confirmed the presence of MTC with vascular invasion, but without lymph node metastases (pT3NoMx according to the 7th edition of the AJCC Cancer Staging Manual). Immunohistochemical staining revealed positive reaction to calcitonin and CD56, whereas the reaction to thyroglobulin remained negative. The Ki-67 was 1%. Staining for SSTR2 and CCK2 showed high cytoplasmic expression in both cases. Knowledge of the presence of CCK2 receptor in MTC patients may be an important indication for the choice of diagnostic and therapeutic procedures. The presence of both the receptor types, cholecystokinin-2/gastrin and somatostatin, is possibly an interesting combination as far as the therapeutic target is concerned.

Rzadki przypadek szpiczaka pozaszpikowego okolicy policzka

Summary It has been presented a rare case of extramedullary plasmocytoma in a 69-years old woman. The tumor has arised in soft tissues of the right cheek. Extramedullary plasmocytoma is a rare tumor which belongs to non-Hodgkins lymphomas. The characteristic feature of that group is monoclonal proliferation of B lymphocytes. One of the most common locations is nasopharynx and paranasal sinuses.

Hemolytic-uremic syndrome: Findings of post-acute renal failure in light and electron microscopy

ABSTRACT The blood count test results of six patients (five male adolescents and one female adult) who were diagnosed with the hemolytic-uremic syndrome are presented. Certain diverse lesions and especially, their different intensity, were observed. They were referred to the clinical process and the time from syndrome occurrence to biopsy.