STUDY OF TUMOR-ASSOCIATED MARKERS AND SOME BIOCHEMICAL INDICATORS IN MELANOCYTIC SKIN FORMATIONS

Author(s):  
A.A. Akhmedova ◽  
E.M. Frantsiyants ◽  
I.A. Goroshinskaya ◽  
V.V. Pozdnyakova ◽  
A.I. Shikhlyarova ◽  
...  

Objective. The purpose of the paper is to study and compare the level of tumor-associated proteins CD44 and S100, indicators of protein and lipid metabolism in melanocytic skin tumors. Materials and Methods. The authors examined 100 samples of 10 % homogenates of skin melanoma tissue, nevi, perifocal zone and resection line. CD44 and S100 levels were determined by enzyme immunoassay using standard test systems on a TECAN analyzer (Austria). The levels of total protein, cholesterol, triglycerides were determined on a ChemWell biochemical analyzer (USA). Results. A sharp increase in S100B level was detected in melanoma tissues, 28 times as high as in the samples of healthy tissue and nevi, as well as a significant, but less evident increase in the CD44 level, which was also observed in nevi tissue. The ratio of albumin and gamma globulins in melanoma and nevi tissues was 3–6 times lower if compared with healthy tissue, and the levels of cholesterol and triglycerides in melanoma were only a little higher than in healthy tissues and nevi. A more than double increase in the γ globulin fraction in melanoma tumor tissue with a decrease in albumin level and the absence of changes in other globulins, as well as a moderate but statistically significant increase in the γ globulin fraction in nevus tissue suggest that the tumor-associated S100B and CD44 markers belong to the γ-globulin fraction. Conclusion. The highly specific increase in S100B level in the supernatant of melanoma tissue homogenates, as well as a less specific increase in CD44 combined with the γ-globulin fraction dominance, suggest that such a correlation is an adverse prognostic sign of tumor progression, which may be important while choosing personalized treatment strategies. Keywords: skin melanoma, nevi, CD44 and S100 tumor-associated markers, tumor tissue homogenates, protein fractions, cholesterol, triglycerides. Цель. Изучить в сравнительном аспекте уровень опухолеспецифических белков CD44 и S100, показателей белкового и липидного обмена в меланоцитарных новообразованиях кожи. Материалы и методы. Объектом исследования были 100 образцов 10 % гомогенатов ткани меланомы кожи, невусов, перифокальной зоны и линии резекции. Уровень CD44, S100 определяли методами иммуноферментного анализа с использованием стандартных тест-систем на анализаторе TECAN (Австрия). Содержание общего белка, холестерина, триглицеридов устанавливали на биохимическом анализаторе ChemWell (США). Результаты. В тканях меланомы выявлено резкое увеличение уровня S100B, в 28 раз превышающего его значение в образцах здоровой ткани и невусов, а также достоверное, но менее выраженное увеличение уровня CD44, которое также наблюдалось в ткани невусов. Соотношение альбуминов и гамма-глобулинов в ткани меланомы и невусов было снижено в 3–6 раз по сравнению со здоровой тканью, а содержание холестерина и триглицеридов в меланоме незначительно превышало их содержание в здоровых тканях и невусах. Более чем двукратное увеличение фракции γ-глобулинов в опухолевой ткани меланомы на фоне снижения уровня альбуминов и отсутствия изменений других глобулинов, а также умеренное, но статистически значимое увеличение фракции γ-глобулинов в ткани невусов позволяют предположить, что изученные нами в качестве онкомаркеров белки S100В и CD44 относятся к фракции γ-глобулинов. Выводы. Высокоспецифичное повышение уровня S100B в надосадочной жидкости гомогенатов ткани меланомы, а также менее специфичное увеличение CD44 в сочетании с доминированием фракции γ-глобулинов позволяют предположить, что подобное соотношение факторов является прогностически неблагоприятным признаком опухолевой прогрессии, что может быть важным при выборе персонализированной тактики лечения. Ключевые слова: меланома кожи, невусы, опухолеспецифические маркеры CD44 и S100, гомогенаты ткани опухоли, белковые фракции, холестерин, триглицериды.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21036-e21036
Author(s):  
Irina A. Goroshinskaya ◽  
Oleg I. Kit ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Viktoria V. Pozdnyakova ◽  
...  

e21036 Background: The high metastatic potential of melanoma and the need for long-term patient monitoring causes the search for tumor markers of this malignant neoplasm. Our aim was a comparative analysis of levels of tumor-specific proteins CD44 and S100 and protein composition in melanocytic lesions of the skin. Methods: We studied 86 samples of cutaneous melanoma and nevus tissues, their perifocal tissues and resection line tissues obtained during tumor excision from 23 patients with cutaneous melanoma pT1-4N0-1M0 and 14 patients with nevi. Intact skin samples obtained from non-cancer patients during reconstructive plastic surgery were used as the comparison group. All patients gave their written informed consent. Levels of CD44 (BenderMedSystems, USA) and S100 (Fujirebio, Sweden) were determined by ELISA in 10% homogenates of all tissues; total protein levels were determined by standard spectrometry and fractional composition of proteins were studied by turbidimetric method. Statistical processing of results was performed using the Statistika 6.0 program with Student’s t-test for two independent groups. Results: Melanoma was characterized by a sharp increase in S100B levels, 28 and 7 times exceeding the levels in intact tissues and nevi. The level of CD44 in melanoma tissue was increased only by 2 times, in nevus tissue - by 48%. The ratio of albumin and gamma globulins in the tissue of melanoma and nevi was 79% and 29% lower than in healthy skin. A more than twofold increase in the gamma globulin fraction in the melanoma tumor tissue against a decrease in albumin and the absence of changes in other globulins, as well as a moderate but statistically significant increase in the gamma globulin fraction in nevi tissue, indicates that S100B and CD44 proteins belong to the gamma globulin fraction. Conclusions: A highly specific increase of S100 levels and a less specific increase of CD44 levels in supernatant liquid of melanoma tissue homogenates, together with the predominance of the gamma globulin fraction, allow considering such factors as a prognostically unfavorable sign of tumor progression, which can be important when choosing a personalized treatment strategy.


2019 ◽  
Vol 65 (5) ◽  
pp. 684-690
Author(s):  
Margarita Barsukova ◽  
Yekaterina Khomutova ◽  
Yevgeniy Khomutov

The article discusses the role of conjugated lactic acid/ lactate anion (LacH/Lac-) and dihydrogenphosphate anion/ hydrogenphosphate anion (H2PO4-/HPO42-) pairs in the formation of the buffer properties of tissue as a factor determining pH. The buffer properties of homogenates of the tissue of adenocarcinoma of the mammary gland and the adjacent tissue were quantitatively characterized by the buffer capacity which was determined by potentiometric titration. The concentrations of acid anions were determined spectrophotometrically. The material was biopsy specimens of mammary gland adenocarcinoma (T1-4, N0-1, M0) and adjacent tissue of 22 patients aged from 33 to 75 years. It was found that the buffer capacity of tumors is in 2.5 times higher than in normal tissue. It was established that for the tumor tissue, the buffer capacity of the LacH/Lac- system is in 3 times higher, and the buffer capacity of the H2PO4-/HPO42-system is in 2.5 times greater than for normal untransformed tissue. Concentrations of lactate anions (1,93 ± 0,50 vs 0,57 ± 0,22; p <0.001) and phosphate anions (2,54 ± 0,39 vs 0,70 ± 0,19; p <0,001) in homogenates of the tumor tissue were significantly higher in tumor tissue in comparison with the adjacent tissue. A strong correlation was found between the concentration of phosphate anions and the buffer capacity for tumor tissue (r = 0,857; p = 0,002) and for adjacent tissue (r = 0,917; p <0,001). The correlation between the concentration of lactate anions and the buffer capacity for tumor tissues can be estimated as average (r = 0,626; p = 0,053), while it is absent for the adjacent tissue (r = 0,494; p = 0,147). The results suggest that the acid-base properties of homogenates of mammary adenocarcinoma tissues are determined by two buffer systems: LacH/Lac- and H2PO4-/HPO42-, while the intracellular acid-base homeostasis of non-transformed tissues is mainly determined by the H2PO4-/HPO42- system.


1990 ◽  
Vol 12 (1) ◽  
pp. 65-72 ◽  
Author(s):  
J. WashüTtl ◽  
R. Viebahn ◽  
I. Steiner
Keyword(s):  

2020 ◽  
Vol 4 (s1) ◽  
pp. 15-15
Author(s):  
A. Colleen Crouch ◽  
Emily A. Thompson ◽  
Mark D. Pagel ◽  
Erik N.K. Cressman

OBJECTIVES/GOALS: The purpose of this work is to investigate natural buffering capacity of liver tissue and tumors, to understand and exploit differences for therapy. Using this work, we will determine the concentrations of reagents (acids or bases) used in ablation treatment to optimize treatment by increasing tumor toxicity and minimizing healthy tissue toxicity. METHODS/STUDY POPULATION: For this preliminary study, two methods will be used: benchtop pH experiments ex vivo and non-invasive imaging using acidoCEST MRI in vivo. For ex vivo, two types of tissues will be tested: non-cancerous liver and tumor tissue from HepG2 inoculated mice (n = 10). After mice are euthanized, pH will be measured in tissue homogenates at baseline and then the homogenates will be placed in either acidic (acetic acid) or basic (sodium hydroxide) solutions with varied concentrations (0.5–10M) and time recorded until pH returns to baseline. For in vivo imaging, Mia PaCA-2 flank model mice (n = 10) will be imaged with acidoCEST MRI to quantify pH at baseline. Mice will then be injected intratumorally with (up to 100 μL of) acid or base at increasing concentrations and imaged to quantify pH changes in the tumor. RESULTS/ANTICIPATED RESULTS: For this study, buffering capacity is defined as the concentration threshold for which tissue can buffer pH back to within normal range. Non-cancerous tissue is likely to buffer a wider range of concentrations compared to tumor tissue. From the benchtop experiment, comparison of time-to-buffer will be made for each concentration of acid/base for the two tissue types. AcidoCEST MRI will provide in vivo buffering capacity and potentially demonstrate tumor heterogeneity of buffering capacity. For both experiments, a pH vs. concentration curve for the two tissue types will allow for comparison of ex vivo to in vivo experiments, which will differentiate contributions of local tissue buffering capacity from the full body’s natural bicarbonate buffer system that depends on respiration and blood flow. DISCUSSION/SIGNIFICANCE OF IMPACT: The pH of the body must be maintained within a narrow range. With cancer, impairment in regulation of tumor metabolism causes acidosis, lowering extracellular pH in tumors. It remains unclear if pH plays a role in local recurrence or tumor toxicity. This work will determine if acidoCEST MRI can measure deliberate alteration of pH and how this change affects biology.


Volume 4 ◽  
2004 ◽  
Author(s):  
Ashvinikumar V. Mudaliar ◽  
Elaine P. Scott

Radio-frequency (RF) ablation is one of the most widely used methods for the treatment of hepatic malignancies. A finite element method (FEM) analysis was employed to determine the thermal dose delivered to the tumor/tissue region. We simulated heating within a RF probe implanted in generic tumor surrounded by healthy tissue using ANSYS. The 3-D model consists of a tumor / tissue region into which the RF probe is embedded inside the tumor. One-quarter symmetry was then invoked. The blood flow was modeled using Penne’s bio-heat transfer equation with differing perfusion rates between the healthy tissue and tumor volume based on literature values. The resulting temperature distribution throughout the region was determined over time. A program was written in Visual Basic to extract the temperature distribution data in the tumor/tissue region and calculate the thermal dose throughout the region. This was done by using a time–temperature Arrhenius relationship for chemical and physical rate process. Tissue necrosis is assumed complete when a thermal dose of one hour has been achieved at 43 °C. In the present study, the geometry of the electrode had a significant effect on the size of the volume of necrosis. It was found that the lower portion of the tumor did not receive the specified thermal dose relative to the upper portion of the tumor in single setting during the RF ablation therapy. This might be due to the Ni-Ti electrode, which protruded only from the top surface of the trocar. The effectiveness of the existing probe can be improved by having one more set of electrodes protruding out from the lower curved surface of the trocar. It was found that the modified probe significantly improved heating in the lower portion of tumor/tissue area, providing more symmetry between the upper and lower portion.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15516-e15516
Author(s):  
Tatiana Zykova ◽  
Oleg Ivanovich Kit ◽  
Yuri Gevorkyan ◽  
Vladislav Legostaev ◽  
Olga A. Bogomolova

e15516 Background: The purpose of the study was to compare the rates of bacterial and fungal colonization of the mucosa in stomach cancer and gastritis. Methods: 59 tumor and healthy tissue samples in stomach cancer and 33 stomach mucosa bioptates in gastritis were studied. DNAs were extracted by the adsorption method. DNAs of Enterobacteriaceae, Staphylococcus spp., Streptococcus spp., Candida spp., Bacteroides spp. were determined by real-time PCR. Results: 40.0% of 30 patients with stomach cancer had adenocarcinoma, 13.3% – signet ring cell carcinoma, 6.7% – undifferentiated cancer, 6.7% – NHL, 3.3% – squamous cell carcinoma, 6.7% – combined signet ring cell carcinoma and neuroendocrine or undifferentiated cancer, 23.3% – combined adenocarcinoma and neuroendocrine, signet ring cell or undifferentiated cancer. The comparison group included 33 patients with morphologically verified superficial gastritis. DNA of Bacteroides spp. was found in tumor and healthy tissues of 80.0% of cancer patients; it was not found in gastritis. DNA of B. fragilis was found in all tumor tissue samples, BFT – in 8.3% of them. The mean amount of Enterobacteriaceae in tumor tissue was 6.7x105 copy/ml, in healthy tissue – 7.0x105 copy/ml, in bioptates in gastritis – 4.0х102 copy/ml; Staphylococcus spp. – 3.4х102 copy/ml, 2.6х102 copy/ml and 8.7х101 copy/ml, Streptococcus spp. – 9.1х105 copy/ml, 1.3х105 copy/ml and 5.1х103 copy/ml, respectively. Thus, the amount of Enterobacteriaceae in tumor tissue in stomach cancer exceeded the value in gastritis by 1675 times, Staphylococcus spp. – by 3.9 times, Streptococcus spp. – by 178 times. Genes of resistance to the penicillin class TEM were found in 50.0% of patients with stomach cancer and in 8.7% of patients with gastritis. DNAs of Candida spp. in stomach cancer were found in 40% of patients in tumor tissue and in 31.0% in healthy tissue, in gastritis – in 8.3% of patients. Conclusions: Enterobacteriaceae and Streptococcus spp., mostly combined, dominate among microflora colonizing gastric mucosa in stomach cancer. The established differences in microbiocenosis in stomach cancer in comparison with gastritis suggest the possible involvement of aerobic and anaerobic microflora in the process of malignant transformation.


Author(s):  
Santhosh Kalash Rajendrakumar ◽  
Adityanarayan Mohapatra ◽  
Bijay Singh ◽  
Chong-Su Cho ◽  
In-Kyu Park

Malignant melanoma is a highly aggressive type of cancer that requires radical treatment strategies to inhibit the cancer cell progression and metastasis. In recent years, preclinical research and clinical trials on melanoma treatment are considerably focused on the adjuvant-based immunotherapy for enhancing the immune response of innate immune cells against cancer cells. However, the clinical outcome of these adjuvant-based treatments are inadequate due to improper delivery system for these immune activators to reach the target site. Hence, we developed a vaccine formulation containing tumor lysate protein (TL) and poly I:C (PIC) complexed with positively charged poly (sorbitol-co- polyethylenimine (PEI)(PSPEI). The resulting ionic PSPEI-polyplexed antigen/adjuvant (PAA) (PSPEI-PAA) nanocomplexes were stable at the physiological condition, non-toxic and&nbsp; enhanced intracellular uptake in immature dendritic cells. In murine B16F10 tumor xenograft model, PSPEI-PAA nanocomplexes significantly suppressed tumor growth and did not exhibit any noticeable sign of toxicity. Additionally, the cytotoxic T lymphocytes (CTLs) assay involving co-culturing of splenocytes isolated from the PSPEI-PAA-treated mice with that of B16F10 cells significantly revealed enhanced cancer killing by the TL-reactivated CTLs compared to untreated control mice bearing tumor. Therefore, we strongly believe that PSPEI-PAA nanocomplexes could be an efficient antigen/adjuvant delivery system and also enhance the antitumor immune response against melanoma tumor in the future clinical trials.


2020 ◽  
Author(s):  
Alyssa D. Schwartz ◽  
Afua Adusei ◽  
Solomon Tsegaye ◽  
Christopher A. Moskaluk ◽  
Sallie S. Schneider ◽  
...  

AbstractIn Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. Emerging data suggest that a large proportion of Ethiopian patients have hormone-positive (ER +) breast cancer. This is surprising given 1) the aggressive nature of the disease, 2) that African Americans with breast cancer frequently have triple negative breast cancer (TNBC), and 3) these patients typically receive chemotherapy, not hormone-targeting drugs. To further examine the similarity of Ethiopian breast tumors to those of African Americans or of those of European descent, we sequenced matched normal and tumor tissue from Ethiopian patients from a small pilot collection. We identified mutations in 615 genes across all three patients, unique to the tumor tissue. Across this analysis, we found far more mutations shared between Ethiopian patient tissue and White patients (103) than we did comparing to African Americans (3). Several mutations were found in extracellular matrix encoding genes with known roles in tumor cell growth and metastasis. We suggest future mechanistic studies on this disease focus on these genes first, toward finding new treatment strategies for breast cancer patients in Ethiopia.


1986 ◽  
Vol 32 (6) ◽  
pp. 1234-1236 ◽  
Author(s):  
R H Christenson ◽  
M W Scroggs ◽  
J D Odom

Abstract Histological examination of supraclavicular lymph node tissue obtained at biopsy from a 63-year-old man disclosed metastatic small-cell carcinoma. On admission and for four days subsequently, total lactate dehydrogenase (LD; EC 1.1.1.27) activity in serum was 6.5 times normal; studies of LD isoenzyme showed persistently increased LD-1, with LD-1 greater than LD-2. Isoenzyme electrophoresis of tissue homogenates prepared from the patient's tumor also showed the LD-1 greater than LD-2 pattern. Isoenzyme studies for supraclavicular lymph node tissue from five control subjects showed contrasting isoenzyme patterns as compared with the patients in whom LD-2, LD-3, and LD-4 predominated. Because these abnormalities were persistent, they differ from the temporal sequence for LD usually seen in myocardial infarction. This emphasizes the importance of repetitive sampling for clinical interpretation of data on this enzyme.


Biomaterials ◽  
2013 ◽  
Vol 34 (38) ◽  
pp. 10209-10216 ◽  
Author(s):  
Mikhail O. Durymanov ◽  
Tatiana A. Slastnikova ◽  
Alexey I. Kuzmich ◽  
Yuri V. Khramtsov ◽  
Alexey V. Ulasov ◽  
...  

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