Ovarian carcinomas (OC) often demonstrate rapid tumor shrinkage upon neoadjuvant chemotherapy (NACT). However, complete pathologic responses are very rare and the mechanisms underlying the emergence of residual tumor disease remain elusive. We hypothesized that the change of somatic BRCA1 status may contribute to this process. The loss-of-heterozygosity (LOH) at the BRCA1 locus was determined for 23 paired tumor samples obtained from BRCA1 germ-line mutation carriers before and after NACT. We observed a somatic loss of the wild-type BRCA1 allele in 74% (17/23) of OCs before NACT. However, a retention of the wild-type BRCA1 copy resulting in a reversion of LOH status was detected in 65% (11/17) of those patients after NACT. Furthermore, we tested 3 of these reversion samples for LOH at intragenic BRCA1 single nucleotide polymorphisms (SNPs) and confirmed a complete restoration of the SNP heterozygosity in all instances. The neoadjuvant chemotherapy for BRCA1-associated OC is accompanied by a rapid expansion of pre-existing BRCA1-proficient tumor clones suggesting that continuation of the same therapy after NACT and surgery may not be justified even in patients initially experiencing a rapid tumor regression.

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The article describes a clinical case of surgical treatment of a patient with multiple primary malignant lesions of the lungs (cancer of the left lung, central peribronchial nodular tumor with involvement of the upper lobe and distal parts of the main bronchus; cancer of the right lung, central tumor with involvement of the upper lobar bronchus). Radical treatment became possible due to using the potential of artifi cial gas exchange of both lungs with two devices with fundamentally different ventilation mechanics. The choice of an optimal tactics for the functional correction of the supposed hypoxemia by volumetric and high-frequency pulmonary ventilation allowed avoiding an imbalance in the ventilation/perfusion ratio and preventing the development of life-threatening complications, as well as ensured an adequate gas exchange for the patient during surgical treatment.

LOSS OF HETEROZYGOSITY AT THE BRCA1 LOCUS AS A MARKER OF SEN- SITIVITY FOR ADJUVANT CHEMOTHERAPY IN HEREDITARY OVARIAN CANCER

Cyclins are a family of regulatory proteins that play a key role in controlling the cell cycle. Abnormalities of cell cycle regulators, including cyclins and cyclin dependent kinases, have been reported in various malignant tumors. Expression of cyclin B1, D1 was investigated with immunohistochemical method in 69 cases of primary ovarian carcinoma. Five-year survival and degree of differentiation have been found to depend on сyclins D1, В1.