Tumor-Infiltrating Lymphocytes in Breast Cancer. Association with Clinical and Pathological Parameters.

In patients with primary resectable breast cancer, a positive correlation between the age and the count of CD16+ lymphocytes and a negative correlation of this parameter with the number of regulatory CD4+CD25+CD127- cells and proliferative activity of Ki-67 tumor cells were revealed. Higher level of Ki-67 was associated with reduced number of effector lymphocytes (CD8+ and CD16+) and elevated content of regulatory CD8+CD11b-CD28- T cells. The absence of expression of estrogen receptors was associated with reduced cytotoxic potential of CD8+ T cell in comparison with ER+ breast cancer. The percentage of CD8+ lymphocytes (CD3+CD8+ and CD8+CD11b+CD28+) among lymphocytes infiltrating the tumor was higher in PR+ breast cancer than in PR- tumors. With increasing the tumor load, the number of lymphocytes expressing CD16 marker and their cytotoxic potential decreased.

CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer.

Overexpression of CD24 is an independent prognostic factor for breast cancer. Recently, two polymorphisms in the CD24 gene were linked to disease risk and progression in autoimmune diseases. Here, we evaluated the clinical relevance of these polymorphisms with respect to their potential to predict a pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC), one of the strongest prognostic factors in this setting. A total of 257 patients were randomized to either doxorubicin/cyclophosphamide (AC) or doxorubicin/pemetrexed (AP), both followed by docetaxel (Doc) as NCT for T2-4 N0-2 M0 PBC as part of an international, multicenter, randomized phase II trial. CD24 polymorphisms were analyzed on germ line DNA and correlated with clinicopathologic variables and pCR. No significant associations were found between either of the polymorphisms and any of the clinicopathologic variables. In a multivariate analysis, CD24 Val/Val genotype was the only significant predictor of pCR (OR: 4.97; P = 0.003). The predictive potential was significant in both treatment arms and in the hormone receptor-positive subgroup. There was no correlation between CD24 3'UTR (TG/Del) genotype and pCR. We did not observe any association between CD24 genotype and CD24 protein expression or in vitro chemosensitivity, but there was a significant correlation between CD24 Val/Val and intratumoral lymphocyte aggregates. In conclusion, CD24 Ala/Val SNP is a strong and independent predictor of pCR after NCT for PBC and may affect immune functions rather than tumor characteristics. Further evaluation of the CD24 function and validation of its predictive potential are clearly warranted.

[Variations of the length of exons and introns in human genome genes].

The exon-intron organization of genes of all human chromosomes was studied in relation to the density of gene distribution on DNA strands and on the number of introns in genes. The lengths of exons, introns and genes have been found to vary correlatively, and this correlation depends on the density of genes in human chromosomes. It has been established that genes with the exon-intron organization have similar tendencies of variation of the lengths of exons and introns with an increase in the number of introns.

[Changes of introns and exons length in genes of arabidopsis, rice, nematode and human].

Genes of Arabidopsis thaliana, Orysa sativa, Caenorhabditis elegans, Homo sapiens have been studied by computer analysis. The average intron and exon lengths in genes of these organisms decreases with increase of intron number in genes. The length of introns and exons in A. thaliana and O. sativa genes is change with increase of intron number in genes by high coefficient of correlation. Linear dependence between the sum of exon lengths and intron number in genes increased proportionally to number of gene introns. The average length of introns and genes of human depend on density of genes in DNA.

[Combination therapy of patients with locally advanced breast cancer]. / Kombinirovannoe lechenie mestnorasprostranennogo raka molochnoi zhelezy.

The investigation involved 30 patients with locally advanced breast cancer (T3-4N1-2M0). Combination therapy comprised two courses: carboplatin 300 mg/m2, i.v., dropwise, on day 1; doxorubicin 30 mg/m2, i.v., bolus-flow, on days 1 and 8; 5-fluorouracil 350 mg/m2, i.v., bolus-flow, on days 1 and 8, and irradiation of the breast and regional metastasis area (single target dose--2 Gy, total target dose--40 Gy). Overall clinical response was 96.7% (29/30), mammography-wise--83.3% (25/30). All patients were found operable and radical mastectomy was performed in 25. Therapeutic effect stage III-IV was histologically confirmed in 40% (25/30), stage I-II--60% (15/25). Median overall and recurrence-free survival was not reached within 36 months in 24/30, relapse-free survival was been reported in 16/24 (66.6%), tumor progression--8/24 (33.4%). Three-year; host-mastectomy recurrence-free survival--68.8 +/- 16.0%.

[Possible use of parameters of tumor cell ploidies and carcinoembryonic antigen levels in the prognostication of epidermoid lung cancer]. / Vozmozhnost' ispol'zovaniia parametrov ploidnosti kletok opukholi i urovnia rakovo-émbrional'nogo antigena dlia prognozirovaniia ploskokletochnogo raka legkogo.

Whether the DNA index (DNAI) of tumor cells and serum carcinoembryonic antigen (CEA) may be used to make prognosis in 78 patients with epidermoid lung cancer at the stage of T1-3 N(o) Mo was studied. There was a direct correlation between tumor ploidy and CEA levels. The two-year relapse- free survival among the operated-on patients at the stage T1-2 N(o) Mo was not shown to be associated with DNAI. At the same time in the T1-3 M1-2 Mo patients radically operated on, the two-year survival correlates with DNAI: it is significantly (p < 0,05) higher in patients with diploid tumors (DNAI = 1.0) than in those with aneuploid cancer (DNAI > 1.05). The patients with low preoperative CEA levels ( < 10 micrograms/l) have a more favourable prognosis after radical surgical treatment.

[Biochemical parameters in the comprehensive diagnosis of lung cancer]. / Biokhimicheskie pokazateli v kompleksnoi diagnostike raka lëgkogo.

Biochemical characteristics of blood serum were studied in 310 patients with lung cancer (stage I-IV), 188 cases of non-malignant pathology od the lung and 35 healthy subjects. Mean levels of total sialic acids, lipid-bound sialic acids, neuron-specific enolase and lactate depydrogenase in blood serum of cancer patients were significantly higher than those in control groups. Mean neuron-specific enolase concentrations in small cell carcinoma of the lung were significantly higher than those in squamous cell and glandular carcinoma and carcinoid. Significant differences were observed for blood serum levels in cases of lung cancer disseminated to the liver and bones, as compared with those without distant metastases. Gamma-glutamyl transferase proced the most sensitive and specific when used for diagnosis of hepatic metastases, while alkaline phospohase--for bone metastases.

[Determining the level of the tumor marker--neuron-specific enolase in patients with neoplastic and non-neoplastic diseases]. / Opredelenie opukholevogo markera--neirospetsificheskoi enolazy u bol'nykh s opukholevymi i neopukholevymi zabolevaniiami.

Radioimmunoassay was employed to measure serum levels of neuron-specific enolase (NSE) in 38 lung cancer patients, 20 patients with noncancer pulmonary lesions and 10 healthy donors. An average NSE level (92.8 +/- 18.7 micrograms/l) in small cell carcinoma (10 patients) was significantly higher (p less than 0.01) than in control, nonmalignant pulmonary diseases, squamous cell and adenocarcinoma. Sensitivity and specificity of the tumor marker to small cell carcinoma reached 80 and 95%, respectively. NSE serum test may serve an additional tool in differential diagnosis of small cell carcinoma of the lung.