Eighty percent of brain metastases (BM) are diagnosed in patients with known primary site of cancer. BM of unknown primary represents a difficult diagnosis. In up to 15 % of patients with BM, the site of the primary tumor will not be detected despite investigations. The prognosis of this entity is very poor. We report here a case of a long survival of a patient with brain metastasis of unknown primary. The conclusion that can be drawn is that within BM of unknown primary exist patients with a very good prognosis that must be collected and published in order to base recommendations.

Background - brain tumors are highly aggressive tumors characterized by secretions of high levels of matrix metalloproteinase-2 and -9, leading to tumor growth, invasion and metastasis by digesting the basement membrane and extracellular matrix components. We previously demonstrated the effectiveness of a nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract in vitro: on activity of urokinase plasminogen activator, matrix metalloproteinases and TIMPs in various human glioblastoma (LN-18, T-98G and A-172) cell lines and on glioblastoma A-172 cell proliferation and Matrigel invasion. Aim - our main objective in this study was to investigate the effect of the NM in vivo on human glioblastoma U-87 MG cell line. Athymic male nude mice inoculated with <$E3~cdot~10 sup 6> U-87 MG cells subcutaneously and were fed a regular diet or a regular diet supplemented with 0,5 % NM. Four weeks later, the mice were sacrificed, the tumors were weighed and measured. The samples were studied histologically. NM inhibited tumor weight and tumor burden by 53 % (p = 0,015) and 48 % (p = 0,010), respectively. Conclusions: these results suggest the therapeutic potential of NM as an adjuvant in the treatment of glioblastoma.

The aim of the work was to investigate the antitumor efficacy of allogeneic tumor vaccine (ATV) modified with rat progenitor neural cell supernatant (RPNS)in rats with glioma 101.8. The study was performed on 74 white randombred rats. ATV was developed on the basis of glioma 101.8 cell suspension modified with RPNS (0,02 or 0,10 mg/ml). RPNS was prepared from suspension made from whole rat brain tissue on 14<^>th (E14) day of gestation. Model of brain glioma 101.8 was reproduced by intracerebral injection of glioma 101.8 cell suspension. ATV was injected intraperitoneally in a volume of 0,2 ml per animal once on the 10<^>th day after tumor transplantation. For survival analysis Kaplan - Mayer multiple assessments method was used. Cytotoxic activity of rat lymphocytes (effector cells) was evaluated in MTT-colorimetric test by determining the state of mitochondrial dehydrogenase enzymes in target cells (allogeneic glioma 101.8 cells). Intraperitoncal administration of ATV modified with 0,10 mg/ml RPNS significantly increased mean survival time and median survival of glioma-bearing rats compared with unvaccinated group (MST (19,9 +- 2,4), 21,4 days; versus MST (14,6 +- 2,8); 14 days; p = 0,0002, Gchan's - Wilcoxon test). Intraperitoncal administration of ATV modified with 0,10 mg/ml RPNS resulted in increased cytotoxic activity of immune cells of rats with glioma in vitro compared with this index in unvaccinated group (p = 0,026, U-Mann - Whitney test). Conclusion: antitumor effect of vaccination with RPNS-modified ATV is realized via increased cytotoxic activity of immune cells, what could be used for further optimization of whole tumor cell vaccine.

Індекс рубрикатора НБУВ: Р569.627.7

Шифр НБУВ: Ж14252 Пошук видання у каталогах НБУВ 

Today, there are conflicting data on the content of cancer stem cells responsible for recurrence and resistance to chemotherapy in tumors of human brain. The aim of the study was to analyze the content of CD133<^>+ cells in different brain tumors by immunofluorescence assay and immunohistochemical method. The samples of different brain tumors removed during neurosurgical operations were studied for CD133 expression. Immunofluorescence assay of tumor imprints revealed CD133<^>+ cells in 40 - 85 % of tumors regardless of histological type. In malignant tumors, the count of CD133<^>+ cells was higher than in benign tumors. Immunohistochemical method used for detection of CD133<^>+ cells was less sensitive than immunofluorescence technique. The number of CD133<^>+ cells may vary even in tumors of the same histological type. In 20 - 30 % of malignant tumors (glioblastomas, medulloblastomas), the content of CD133<^>+ cells was very low or not detected at all. Conclusions: in tumors of the brain of different genesis and degree of anaplasia CD133<^>+ cells are found out. In malignant tumors (glioblastomas and medulloblastomas), CD133<^>+ cells are much more frequently detected than in benign brain tumors. The content of CD133<^>+ cells in brain tumors is highly variable being small and some malignant tumors, indicating low predictive and diagnostic value of cancer stem cell content in clinical practice.

It is known that metformin is a hypoglycemic drug used to treat type II diabetes mellitus. Recently active studies of its antitumor activity in relation to different types of malignant cells are conducted. Aim - to determine the relationship between cytotoxic activity of metformin in vitro and its antitumor activity in vivo. The rat C6 glioma cell line and mouse Lewis lung carcinoma cells (LLC) were used in this work. The number of living cells in the cytotoxic test was evaluated using sulforhodamine B. Parameters of tumor cell susceptibility to metformin activity in vitro were calculated using nonlinear and linear regression of experimental data. The antitumor action of metformin in vivo was evaluated routinely by the extension of survival time (ST) (in rats with intracerebral C6 glioma) and its effect on the volume of the primary tumor, the number and volume of metastases (in mice with LLC). Results: In cultured LLC cells in vitro, the proportions of metformin-resistant (A1 %) and metformin-sensitive (A2 %) subpopulations were 10,0 +- 2,2 % and 92,0 +- 3,5 %, respectively, in terms of the total number of living cells. Parameter t, which characterizes the sensitivity of cancer cells to metformin action (the lower is the value of this parameter the higher is sensitivity of cells to metformin cytotoxicity), for metformin-resistant and metformin-sensitive subpopulations was: <$Et sub 1 (mM)~=~inf> and t2(mM) = 2,9 +- 0,3, correspondingly. For metformin-sensitive subpopulation of LLC cells IC50 (mM) = 2,42 +- 0,34. The volume of the primary tumor, the amount and volume of metastases in mice receiving metformin at a dose of Dmin (0,15 g/kg) and Dmax (0,3 g/kg) values did not significantly differ from those in the control. However, in the case of Dmin, there was a tendency to increased volume of the primary tumor, in the case of Dmax, there was a tendency to increased volume of metastases. The analogical parameters (A1, A2, b1, b2, IC50 (1), IC50 (2)) characterizing cell sensitivity to the action of metformin in vitro were obtained in relation to C6 glioma cells. In metformin-resistant subpopulation, these parameters were: A1 (%) = 72,3 +- 1,4; b1 (%/mM) = 0,43 +- 0,005; IC50 (1) (mM) = 84,1 +- 2,4. For metformin-sensitive subpopulation, these parameters were: A2 (%) = 30,8 +- 2,3; b2 (%/mM) = 2,87 +- 0,4; IC50 (2) (mM) = 5,37 +- 0,45. In vivo, a statistically significant anti-glioma effect of metformin was observed: at a dose of Dmax (5,2 g/kg) administration of this preparation resulted in a prolongation of the mean ST of tumor-bearing rats by 23 % (p << 0,05) compared with that in the control. Conclusions: we found no correlation between the cytotoxic/cytostatic action of metformin in vitro and its antitumor activity in vivo on the two types of tumor cells; these results indicate a significant contribution of the tumor microenvironment to the implementation of the antitumor activity of the drug.

Індекс рубрикатора НБУВ: Р569.627.7

Рубрики:

Пухлини головного мозку та його оболонок

Шифр НБУВ: Ж21341/а Пошук видання у каталогах НБУВ 

Исследована инфицированность опухолей головного мозга человека ДНК полиомавирусов. Исследование проведено с использованием метода полимеразной цепной реакции на 65-ти образцах ткани опухолей головного мозга (57 - нейроэктодермального, 4 - мезенхимального генеза). Установлена высокая частота инфицированности глиом головного мозга (олигодендроглиом - в 66,7 % случаев, олигодендроастроцитом - в 66,7 %, глиобластом - в 40 %) ДНК полиомавирусов JCV, BKV, SV-40. В метастазах опухолей центральной нервной системы вирусной инфекции не выявлено. Не установлено и корреляции между частотой заражения полиомавирусами и степенью злокачественности опухолей. Полученные данные свидетельствуют о целесообразности проведения вирусологического исследования опухолей головного мозга и спинномозговой жидкости.

Мета дослідження - вивчення впливу багатого на пролін поліпептиду (ПБП) на стовбурові клітини строми кісткового мозку in vivo та in vitro і лінії пухлинних клітин. Застосовано методи виділення стромальних клітин гігантоклітинної пухлини (ГКП) і одержання штамів цих клітин, а також штамів стромальних клітин нормального кісткового мозку, введення ПБП щурам, експлантація в культуру кістковомозкових клітин, додавання ПБП у культури клітин. Різні способи і дози введення ПБП щурам збільшують концентрацію мультипотентних мезенхімальних стромальних клітин (ММСК) у кістковому мозку. Додавання ПБП у культури ММСК нормального кісткового мозку призводить до зростання проліферативної активності клітин у 1,5 - 2,5 разу, внесення ПБП у культури ММСК ГКП інгібує проліферацію клітин у 1,5 - 2 разу. У культурах пухлинних клітин спостерігається як пригнічення пухлинних клітин, так і відсутність впливу поліпептиду на проліферацію. Висновки: введення ПБП щурам підвищує концентрацію ММСК у нормальному кістковому мозку, а за додавання ПБП у культуру тканин виявлено його різноспрямовану дію на проліферацію клітин.

Background: anticancer action of sodium dichloroacetate (DCA) could be related to its ability to activate oxidative phosphorylation leading to enhanced generation of reactive oxygen species and induction of apoptosis. On the other hand, activation of oxidative phosphorylation could promote tumor cell survival, in particular, via increased ATP synthesis. Such ambiguous effects of DCA could influence its anticancer effectiveness, depending on biological properties of a tumor, schedule of DCA administration and its dosage. The aim of the study was to analyze anticancer effect of DCA against glioma C6 in rats under conditions of different schedules of its administration and various dosages. The study was carried out in Wistar rats with intracerebrally transplanted glioma C6 cells. Therapy with DCA was performed as follows: daily for 6 days starting from the second day after tumor cell transplantation (schedule I) or 7<^>th day (schedule II) at a dose of 1,0 g/kg, or daily for 13 days starting from the second day at doses of 1,0; 1,5 or 4,5 g/kg (schedule III). An influence of hypoxia on anticancer effect of DCA was studied using hypoxic chambers where oxygen content was maintained at a level of 12,5 +- 13 % for 3 h after DCA administration to glioma C6 bearing rats. The state of mitochondrial electron transport chain components in tumor cells was studied using electron paramagnetic resonance. It has been shown that therapy with DCA using schedule I resulted in 15 % decrease of animals life span (LS; p << 0,05), while the use of schedule II had no effect on this index. Prolonged administration of DCA (schedule III) resulted in significant antitumor effect and increased LS of rats by 25,5 % (p << 0,05). Under hypoxic conditions, treatment with DCA resulted in a significant increase of animal LS by 15 - 22 %. Dosage of DCA had a moderate effect of its anticancer action. Maximal effect, an increase of LS by 34,5 % (p << 0,05) was detected at a dose of 1,5 g/kg. It has been shown that anticancer activity of DCA under all studied conditions is not related to its influence on a functional state of tumor cell mitochondria. Conclusion: anticancer effect of DCA significantly depends on a schedule of its administration; being administered at equal total dose, but dependent on the schedule DCA could cause ambiguous effects varying from tumor growth stimulation to significant anticancer activity. Under hypoxic conditions, anticancer efficacy of DCA against glioma C6 is significantly enhanced.

The aim of this study was to investigate the low-power density sonication, sonodynamic therapy (SDT) with Photolon and combination of SDT and photodynamic therapy (PDT) with Photolon for the ablation of glioma C6 tumor model in rats. The study was performed on 50 rats bearing glioma C6. The tumors were sonicated with/without prior intravenous injection of photosensitizer (PS) Photolon (2,5 mg/kg b.w). Sonication was performed with 0,4; 0,7 and 1,0 W/cm² power density at 1 MHz frequency for 10 min, 2,0 h after Photolon administration using BTL-5710 Sono (BTL Industries Limited, Great Britain). PDT was carried out 2,5 h after Photolon administration using diode laser with 661 nm wavelength (IMAF-AXICON, Minsk, Republic of Belarus) at doses of 50 and 100 J/cm² with 0,17 W/cm² fluence rate. Assessment of tumor response was performed by vital staining with Evans blue and pathologic examination. The maximal tumor necrosis area that underwent sonication (1 MHz; 0,7 W/cm²; 10 min.) followed by PDT at a dose of 100 J/cm² was 100 %. Conclusion: this is the first report to demonstrate the benefits of sono-photodynamic therapy (SPDT) consisting of low-power density ultrasound and PDT for the treatment of malignant glioma models.

Отмечено, что клиническую резистентность глиобластом к химиотерапии можно объяснить действием насосов, откачивающих препараты, подобные P-гликопротеину, которые играют важную роль в снижении эффективности лекарственных средств. Изучена возможность применения эпотилона B, не являющегося субстратом для P-гликопротеина, для воздействия на глиобластомные клетки. Для оценки эффективности эпотилона B как антинеопластического препарата в работе in vitro использованы клеточные линии глиобластомы, отличающиеся по статусу p53. Для оценки уровня экспрессии тубулина и сурвивина в клетках, обработанных эпотилоном B, использованы методы иммунофлуоресценции и ELISA. Окрашивание акридиновым оранжевым применено для детекции погибших клеток после обработки эпотилоном B. Сделаны выводы, что эпотилон B вызывает различный противоопухолевый ответ в клетках глиобластомы, экспрессирующих мутантный p53, либо отрицательных по p53. Это позволяет предположить, что эпотилон B является альтернативой классическим препаратам, ингибирующим микротрубочки (например винкристину, паклитакселу), которые используют в клинической практике при лечении глиобластом с мутантным белком p53.

Індекс рубрикатора НБУВ: Р569.627.7

Рубрики:

Шифр НБУВ: Ж14252 Пошук видання у каталогах НБУВ 

Індекс рубрикатора НБУВ: Р569.627.7

Рубрики:

Пухлини головного мозку та його оболонок

Шифр НБУВ: Ж14252 Пошук видання у каталогах НБУВ 

Objective: investigating the distinctions pharmacokinetics of chlorin e6 conjugated with polyvinyl pyrrolidone photosensitizer (Ce6CPPPS) in healthy and tumor tissues of rat brain and evaluating the antitumor efficacy of combination treatment for C6 rat glioma including photodynamic (PDT) and antiangiogenic therapy (AAT). The study was performed on 50 white random-bred rats in subcutaneous and intracranial models of C6 glioma. Photosensitizer (PS) Ce6CPPPS single injection at a dose of 2,5 mg/kg was made into the animal's caudal vein. The PS accumulation level in brain tissues and C6 rat glioma was measured with spectral fluorescence technique using LESA-01-Biospek spectrum analyser (Russian Federation, Moscow; lambda = 632,8 nm). Photoirradiation of intracranial and subcutaneous C6 glioma was carried out with a light exposure dose of 50 J/cm<^>2 (IMAF-Axicon, Republic of Belarus; lambda = 661 nm). AAT drug bevacizuntab, single injection was made intravenously at a dose of 10 mg/kg 24 h after tumor photoirradiation. The criteria for efficacy evaluation were mean survival time (MST) and median survival of the animals in the study group vs the control and the percentage of tumor necrosis areas induced by the above-mentioned treatment. The optimal time for photoirradiation of intracranial C6 glioma is 0,5 h after Ce6CPPPS injection. The combination therapy group demonstrated a statistically significant MST increase (38,4 +- 4,39 days) compared with the PDT group (29,2 +- 3,5 day's) (p = 0,02) and the AAT group (27,1 +- 2,74 days) (p = 0,02). Necrosis areas in tumor tissue were as follows: the intact control - 10,0 +- 2,55 %, PDT - 54,87 +- 6,95 % (p = 0,003), AAT - 57.83 +- 6,53 % (p = 0,003) and combination therapy - 89,43 +- 5,57 % (p = 0,001). Conclusions: this paper is the first report about feasibility of efficient use of PDT with a PS of chlorin series and AAT with bevacizumab for the treatment of brain tumors in experimental models.

Індекс рубрикатора НБУВ: Р569.627.7

Рубрики:

Пухлини головного мозку та його оболонок

Шифр НБУВ: Ж14252 Пошук видання у каталогах НБУВ 

Індекс рубрикатора НБУВ: Р569.627.7

Рубрики:

Пухлини головного мозку та його оболонок

Шифр НБУВ: Ж14252 Пошук видання у каталогах НБУВ 

Aim - recent technologic advances have led to the development of frameless radiosurgery. We report our initial results using frameless image-guided radiosurgery for the management of brain metastases. Over a 2-year period, 16 patients harboring 28 lesions were treated in our institution. 12 of 16 patients were treated in a single fraction, but 4 patients were treated using fractioned stereotactic radiotherapy in 3 - 5 fractions. The maximum target diameter, as determined by T1 - weighted contrast - enhanced magnetic resonance imaging were << 4 cm in all patients. 8 patients (50 %) received WBRT (3 Gy in 10 fractions to a total dose of 30 Gy) prior to stereotactic radiosurgery, and were treated with SRS for either lesion progression or new lesions. The total treatment volume for each patient was the sum of the treatment volumes for all treated metastases. The median total treatment volume was 18,63 cm³ (range 1,85 - 47,03 cm³). Median overall survival time of entire group were 10 months (95 % confidence interval 7,470 - 12,530 months). Of the 3 (11,11 %) lesions that showed complete response, all were associated with breast cancer. Partial response was seen in 8 (29,62 %) cases. Stable disease was seen in 13 (48,14 %) cases, but 3 (11,11 %) cases showed progression of disease. Conclusion: further studies are needed to to match the treatment results with other available modalities to optimize and individualize care of patients with brain metastases.

Індекс рубрикатора НБУВ: Р569.627.7

Рубрики:

Пухлини головного мозку та його оболонок

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ