Cancer microcell initiation and determination.

BACKGROUND: Cancer remains one of the leading causes of death worldwide, despite the possibilities to detect early onset of the most common cancer types. The search for the optimal therapy is complicated by the cancer diversity within tumors and the unsynchronized development of cancerous cells. Therefore, it is necessary to characterize cancer cell populations after treatment has been applied, because cancer recurrence is not rare. In our research, we concentrated on small cancer cell subpopulation (microcells) that has a potential to be cancer resistance source. Previously made experiments has shown that these cells in small numbers form in specific circumstances after anticancer treatment. METHODS: In experiments described in this research, the anticancer agents' paclitaxel and doxorubicin were used to stimulate the induction of microcells in fibroblast, cervix adenocarcinoma, and melanoma cell lines. Mainly for the formation of microcells in melanoma cells. The drug-stimulated cells were then characterized in terms of their formation efficiency, morphology, and metabolic activity. RESULTS: We observed the development of cancer microcells and green fluorescent protein (GFP) transfection efficiency after stress. In the time-lapse experiment, we observed microcell formation through a renewal process and GFP expression in the microcells. Additionally, the microcells were viable after anticancer treatment, as indicated by the nicotinamide adenine dinucleotide hydrogen phosphate (NADPH) enzyme activity assay results. Taken together, these findings indicate that cancer microcells are viable and capable of resisting the stress induced by anticancer drugs, and these cells are prone to chemical substance uptake from the environment. CONCLUSION: Microcells are not only common to a specific cancer type, but can be found in any tumor type. This study could help to understand cancer emergence and recurrence. The appearance of microcells in the studied cancer cell population could be an indicator of the individual anticancer therapy effectiveness and patient survival.

Morphological and Immunocytochemical Characterization of Paclitaxel-Induced Microcells in Sk-Mel-28 Melanoma Cells.

Biomarkers, including proteins, nucleic acids, antibodies, and peptides, are essential for identifying diseases such as cancer and differentiating between healthy and abnormal cells in patients. To date, studies have shown that cancer stem cells have DNA repair mechanisms that deter the effects of medicinal treatment. Experiments with cell cultures and chemotherapy treatments of these cultures have revealed the presence of small cells, with a small amount of cytoplasm that can be intensively stained with azure eosin, called microcells. Microcells develop during sporosis from a damaged tumor macrocell. After anticancer therapy in tumor cells, a defective macrocell may produce one or more microcells. This study aims to characterize microcell morphology in melanoma cell lines. In this investigation, we characterized the population of cancer cell microcells after applying paclitaxel treatment to a Sk-Mel-28 melanoma cell line using immunocytochemical cell marker detection and fluorescent microscopy. Paclitaxel-treated cancer cells show stronger expression of stem-associated ALDH2, SOX2, and Nanog markers than untreated cells. The proliferation of nuclear antigens in cells and the synthesis of RNA in microcells indicate cell self-defense, promoting resistance to applied therapy. These findings improve our understanding of microcell behavior in melanoma, potentially informing future strategies to counteract drug resistance in cancer treatment.

Surgical Treatment of Hepatocellular Carcinoma with a Tumor Thrombus Invading the Right Atrium: A Case Report.

Up to 3% of all hepatocellular carcinomas (HCCs) present with a tumor thrombus (TT) in the inferior vena cava (IVC) and right atrium (RA). Extensive growth of HCC into the IVC and the RA is associated with a particularly poor prognosis. This clinical condition is related to a high risk of sudden death due to pulmonary embolism or acute heart failure. Therefore, a technically challenging treatment undergoing hepatectomy and cavo-atrial thrombectomy is necessary. We report a 61-year-old man presenting with right subcostal pain, progressive weakness, and periodic shortness of breath for 3 months. He was diagnosed with advanced HCC with a TT extending from the right hepatic vein into the IVC and RA. A multidisciplinary meeting with cardiovascular and hepatobiliary surgeons, oncologists, cardiologists, anesthesiologists, and radiologists was held to determine the best treatment approach. Initially, the patient underwent right hemihepatectomy. As follows, the cardiovascular stage using cardiopulmonary bypass was successfully performed, removing the TT from the RA and ICV. In the early postoperative period, the patient remained stable and was discharged on the 8th postoperative day. A morphological examination revealed grade 2/3 HCC, a clear cell variant with microvascular and macrovascular invasion. Immunohistochemical staining was positive for HEP-1, CD10, whereas negative for S100. The morphological and immunohistochemical results corresponded to HCC. The treatment of such patients requires the cooperation of various specialties. Although the approach of the surgery is extremely complex including specific technical support, as well as high perioperative risks, the result offers favorable clinical outcomes.

Doxorubicin and paclitaxel versus fluorouracil, doxorubicin and cyclophosphamide as first-line therapy for women with advanced breast cancer: long-term analysis of the previously published trial.

BACKGROUND: The aim of this study was to perform an independent review of the efficacy data and to determine whether the efficacy difference observed in a phase III randomised clinical trial that compared doxorubicin plus paclitaxel (AT) versus fluorouracil/doxorubicin/cyclophosphamide (FAC) in first-line chemotherapy of metastatic breast cancer was maintained after a longer follow-up period. MATERIAL AND METHODS: A blinded independent review of original radiological images and original case report forms (CRFs) was conducted by an expert radiologist and an expert medical oncologist, respectively. The analysis of the updated data included time to progression (TTP) and overall survival (OS). RESULTS: CRFs for all 267 patients randomised in the study were available for medical review. The results of the independent review were consistent with the original analysis. At a median follow-up of 69 months, the difference in median TTP and OS in favour of the AT arm remained significant (median TTP 8.1 vs. 6.2 months, (p = 0.036); OS 23.0 vs. 18.3 months, (p = 0.005), respectively). CONCLUSIONS: This blinded independent review and analysis of updated data confirmed the advantage for AT over FAC with regard to TTP and OS in patients with metastatic breast cancer.

Analysis of cardiac and pulmonary complication probabilities after radiation therapy for patients with early-stage breast cancer.

OBJECTIVE: The purpose of this study was to evaluate the radiobiological implications of clinical use of respiratory-gated techniques for postoperative radiation therapy of early-stage left-sided breast cancer after breast-conserving surgery. MATERIAL AND METHODS: Radiation therapy treatment plans of 80 patients with early-stage breast cancer (stage I-II), receiving whole breast irradiation after breast-conserving therapy, were analyzed. The control group consisting of 47 patients received standard radiation therapy, and the respiratory-gated group consisting of 33 patients received deep inspiration-gated radiation therapy. Normal tissue complication probabilities (NTCP) for cardiac mortality and for clinical radiation-induced pneumonitis were calculated for all patients included in present study, using relative seriality model. NTCP data were analyzed for 113 radiation therapy plans, which included free breathing plans for the respiratory-gated groups. RESULTS: Pneumonitis probability was 0.6% (range 0.0-2.8%) and 0.3% (0.0-1.2%) for control and respiratory-gated group, respectively. Cardiac mortality was 1.3% (0.0-5.0%) and 0.2% (0.0-2.8%) for control and respiratory-gated group, respectively. Using respiratory-gated radiation therapy, NTCP was reduced in comparison with the control group by 83% (P<0.00001) and by 55% (P=0.01270) for cardiac mortality and for clinical radiation-induced pneumonitis, respectively. CONCLUSIONS: Use of respiratory-gated radiation therapy, for postoperative treatment of early-stage breast cancer, significantly reduces excessive cardiac mortality probability and pulmonary complication probability, as compared to standard radiation therapy techniques. This is especially important from heart complication probability point of view, as cardiac mortality remains one of the important issues of postoperative breast irradiation in patients with early stage breast cancer.