When dormancy fuels tumour relapse

Tumour recurrence is a serious impediment to cancer treatment, but the mechanisms involved are poorly understood. The most frequently used anti-tumour therapies—chemotherapy and radiotherapy—target highly proliferative cancer cells. However non- or slow-proliferative dormant cancer cells can persist after treatment, eventually causing tumour relapse. Whereas the reversible growth arrest mechanism allows quiescent cells to re-enter the cell cycle, senescent cells are largely thought to be irreversibly arrested, and may instead contribute to tumour growth and relapse through paracrine signalling mechanisms. Thus, due to the differences in their growth arrest mechanism, metabolic features, plasticity and adaptation to their respective tumour microenvironment, dormant-senescent and -quiescent cancer cells could have different but complementary roles in fuelling tumour growth. In this review article, we discuss the implication of dormant cancer cells in tumour relapse and the need to understand how quiescent and senescent cells, respectively, may play a part in this process.

Migraine as the First Symptom for Setting a Clinical Diagnosis

The migraine is among the most frequent complains of the patients requesting a medical consultation. I am presenting hereby the case of a 34-year old patient, who complained of diffuse migraine followed several weeks later by vomiting and seizures. The brain computed tomography (CT) and magnetic resonance imaging (MRI) examinations indicate an intracranial spread located in the left (temporal) hemisphere, which had a mass effect on the ventricular system. When performing the extemporaneous examination, it was found an anaplastic oligodendroglioma. Subtotal resection under microscopic guidance was performed, as well as radiotherapy and chemotherapy after the surgery. When discharged from hospital, the patient was surgically cured and had an improved neurological state. The repeated checkups (clinical and paraclinical) indicated no signs of local relapse. Approximately 8 years after the first surgery, the patient returned for a check-up, in view of investigations and treatment, while complaining of migraine and a nervousness state that was bothering his family. The brain MRI indicated a large tumour relapse located in the left temporal-hippocampal region. The histopathology examination indicated that it was an anaplastic oligodendroglioma relapse. Surgery was performed and the tumour relapse located in the left temporal-hippocampal region was completely ablated. After the surgery, the patient was conscious and had no movement dysfunctions.

IMMUNOHISTOCHEMICAL AND GENETIC PROGNOSTIC FACTORS OF NEOADJUVANT CHEMORADIOTHERAPY EFFICАCY IN PERSONALIZED TREATMENT OF LOCAL ADVANCED RECTAL CANCER

The aim: The aim of our study was to define the factors that can robustly predict a response to neoadjuvant chemoradiotherapy (NCRT) in patients with local advanced rectal cancer (LARC) and prognosis factors of progression free survival (PFS) using molecular (8-oxodGu), immunohystochemical (Ki-67) and genetic (GSTP1 and MTHFR genes polymorphism) markers. Materials and methods: GSTP1 and MTHFR polymorphisms were studied by real-time PCR on tumour material from 110 patients with LARC. Ki-67 protein expression was assessed using rabbit monoclonal antibodies to Ki-67 (Dako, Denmark) on EnVisionTM FLEX detection system (Dako, Denmark). 8-oxodGu level in eluate was measured by spectrophotometry. Results: Patients from both groups showed significant pathomorphological response to NCRT. It is robust correlation between 8-oxodGu levels in patients’ blood and their response to CRT (mrTRG scale) in MG was determined. Oxaliplatin-containing chemotherapy promotes statistically significant decrease of 8-oxodGu levels. With the decrease of Ki-67 protein expression level the probability of tumour relapse increases. It is determined that critical value of Ki-67 protein expression level makes less than 27 and tumour relapse probability in this case makes 50%. Tumour relapse risk in patients with GSTP1 and MTHFR polymorphism is 12.3 and 16.3 times higher than in patients who do not carry such polymorphism, respectively. Combination of GSTP1, МTНFR polymorphisms and Кі-67 protein expression factors determines prognostic probability of tumour relapse within 51-99%. Conclusions: 8-oxodGu level can serve as independent prognostic factor of NCRT efficacy in patients with LARC. Combination of GSTP1, МTНFR genes polymorphism with Кі-67 protein expression decrease enables monitoring and robust prognosis of LARC relapse.

Peri - and Intraocular Mutilating Advanced Squamous Cell Carcinoma: ʺMonsters Inside Your Bodyʺ?

Periocular malignancies represent between 5% and 10% of all types of skin cancers. The incidence of eyelid (but also the periocular located) malignancies seems to differ in distribution across the continents. The incidence of eyelid tumours (but also the periocular located tumours) in a predominantly white population determined that BCC is the most common malignant periocular eyelid tumour in whites. This finding has been replicated consistently throughout the literature, with BCC representing 85–95% of all eyelid malignancies, SCC representing 3.4 - 12.6%, Seb Ca representing 0.6 - 10.2%, and both melanoma and Merkel cell carcinoma representing less than 1%. Most periocular skin cancers are associated with ultraviolet radiation (UVR) exposure. Ultraviolet radiation causes local immune suppression, which, coupled with DNA abnormalities in tumour suppressor genes and oncogenes, leads to the development of skin cancers. We are presenting a 62 - year - old patient with a small nodule about 2 cm away from the lower lid of his left eye. A tumour was surgically treated. Several years later there was a tumour relapse, treated with radiotherapy and subsequent chemotherapy with Endoxan and Cisplatin. After the second relapse, he was treated surgically in general anaesthesia by orbital exenteration, removal of the orbital floor and resection of zygomatic bone and the maxillary sinus. A couple of months later, he developed a tumour relapse in the scars and the area of a primary tumour with tumour progression. A possible therapy with Cetuximab or radiation therapy was discussed as a possible treatment option.