AIMTo investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODSAGS (gastric cancer cell line), Caco-2 (colon cancer cell line) and T3M4 (pancreatic cancer cell line) were treated by cisplatin and different temperature setting (37 °C to 45 °C) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTSAGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 °C to 41 °C in neither cancer cell line. However, a temperature of 43 °C enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 °C by 30%, 20%, and 18% in AGS, Caco-2, and T3M4 cells, respectively.CONCLUSIONIn addition to cisplatin, hyperthermia up to 43 °C does not affect the viability of cancer cells in a synergistic manner.
Our investigation of OVCAR-3 cells critically disputes the benefit of hyperthermia in ovarian cancer treatment. Further in vitro and in vivo research is essential for better understanding of the mechanisms of action of hyperthermia and its role in the treatment of epithelial ovarian cancer.
We report a unique clinical case about an 18-year-old woman, immediately post-partum after an urgent C-section, who survived severe sepsis, acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) and was successfully treated with 11 different antibiotics, massive blood transfusions and repetitive surgeries and was on extracorporeal membrane oxygenation (ECMO) support for 22 days. Although, ECMO is a time-limited procedure and most manufacturers do not advise more than 14 days of use, the situation for this patient was life-threatening and ECMO, despite the dangerous risks listed above, was the only way to win time for the lungs to recover and for treatment of the underlying disease, while maintaining adequate oxygenation and circulation. Fortunately, the condition of this woman was stabilized and she achieved complete physical recovery, despite minor neurological deficit in the fingers of her right hand.
Precancerous lesions of human cervix uteri have a tendency for regression or progression. In cervical intraepithelial neoplasia grade 2 (CINII) case there is an uncertainty if a lesion will progress or regress. The carbonic anhydrase IX (CAIX) enzyme is overexpressed in cervical cancer which is more sensitive to radiotherapy. CAIX is associated with poor prognosis in solid hypoxic tumors. The aim of this study was to determine factors related to elevated soluble CAIX (s-CAIX) in high-grade intraepithelial lesion (HSIL) cases. Methods. Patients diagnosed with HSIL (N = 77) were included into the research group whereas without HSIL (N = 72)—the control group. Concentration of the soluble CAIX (s-CAIX) in plasma was determined by the DIANA ligand-antibody-based method. C. trachomatis was detected from cervical samples by PCR. Primary outcomes were risk factors elevating s-CAIX level in HSIL group. Non-parametric statistical analysis methods were used to calculate correlations. Results. The s-CAIX level in patients with HSIL was elevated among older participants (rs = 0.27, p = 0.04) and with C. trachomatis infection (p = 0.028). Among heavy smokers with HSIL, the concentration of s-CAIX was higher in older women (rs = 0.52, p = 0.005), but was not related to the age of heavy smokers’ controls (τ = 0.18 p = 0.40). Conclusion. The concentration of s-CAIX was higher among older, heavy smoking and diagnosed with C. trachomatis patients. All these factors increased the risk for HSIL progression.
Tyrimo tikslas. Įvertinti hiperterminės chemoterapijos, naudojant cisplatiną, in vitro poveikį OVCAR-3 kiaušidžių vėžio ląstelėms ir poveikio pokyčius, slopinant HO-1. Tyrimo metodai. Eksperimentinis tyrimas, kurio metu LSMU MA Virškinimo sistemos tyrimų instituto Chirurginės gastroenterologijos laboratorijoje atlikti tyrimai, naudojant epitelinės kiaušidžių adenokarcinomos ląstelių liniją OVCAR-3. Imituojant hiperterminės chemoterapijos sąlygas, ląstelės paveiktos hipertermija ir cisplatina, slopinant ir neslopinant HO-1. Tirtas ląstelių gyvybingumas, apoptozė, proliferacija. Rezultatai. Hipertermija iki 43 °C nedaro įtakos OVCAR-3 ląstelių gyvybingumui ir apoptozei, o 43 °C ir aukštesnė temperatūra sustiprina cisplatinos citotoksinį poveikį. Cisplatinos poveikis OVCAR-3 ląstelėms tiesiogiai priklauso nuo dozės. Citoprotekcinio baltymo HO-1 raišką OVCAR-3 ląstelėse didina cisplatinos poveikis. HO-1 slopinimas pagerina citotoksinį hiperterminės chemoterapijos poveikį OVCAR-3 ląstelėms – sumažina gyvybingumą ir padidina apoptozę. Išvada. Žemesnė nei 43 °C temperatūra nei viena, nei kartu su cisplatina reikšmingo poveikio kiaušidžių vėžio ląstelių gyvybingumui nedaro. Nors hipertermija nedidino HO-1 raiškos, HO-1 nuslopinimas labiausiai sustiprino kompleksinį 43 °C hipertermijos ir cisplatinos poveikį kiaušidžių vėžio ląstelių gyvybingumui ir apoptozei.
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