RESUMEN
We performed comparative analysis of quantitative changes in the populations of bone marrow microenvironment cells in patients with chronic myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia in the debut, during response to chemotherapy, and during relapse/progression/loss of response. It was shown that in the active phase of hemoblastoses, the number of reticular cells and fibroblasts in trephine biopsy specimens was higher than in the phase of response to chemotherapy and than in the control group. In patients with relapse of multiple myeloma and loss of response in chronic myeloid leukemia, the percentage ratio of adipocytes in the bone marrow significantly (by 9-13-fold) increased. In addition, endotheliocytes appear in the active phase of all hemoblastoses in trephine biopsy specimens, while in the phase of response to chemotherapy and in the control group, these cells were absent. The revealed quantitative changes in bone marrow stromal cells can be taken into account during assessing the phase of hemoblastosis and effectiveness of chemotherapy.
Asunto(s)
Antineoplásicos/farmacología , Médula Ósea/patología , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Mieloma Múltiple/metabolismo , Microambiente Tumoral , Biopsia , Médula Ósea/fisiología , Proliferación Celular , Citocinas/metabolismo , Femenino , Fibroblastos/citología , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de NeoplasiaRESUMEN
Immunohistochemical and morphometric analysis of the microcirculatory bed in the tumor and non-tumor parenchyma of the prostate was carried out with the use of endothelial cell marker CD34 in patients treated by high-intensity focused ultrasound (HIFU). The numerical density of microvessels in the adenocarcinoma focus did not correlate with the degree of its differentiation, while high values of this parameter were associated with lower incidence of local progression after HIFU. Effective HIFU ablation led to progressive fibrosis and significant reduction of the microcirculatory bed in zones of intact non-tumor glands in control samples; an inverse relationship between the degree of reduction of the microcirculatory bed and the probability of relapse was revealed. The use of HIFU in combination with androgen deprivation was associated with a decrease in numerical density of microvessels in zones of tumor and non-tumor parenchyma in patients with relapses.
Asunto(s)
Adenocarcinoma/irrigación sanguínea , Flutamida/uso terapéutico , Goserelina/uso terapéutico , Ultrasonido Enfocado de Alta Intensidad de Ablación , Próstata/irrigación sanguínea , Neoplasias de la Próstata/irrigación sanguínea , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , Antígenos CD34/genética , Antígenos CD34/metabolismo , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Fibrosis , Estudios de Seguimiento , Humanos , Masculino , Microcirculación/efectos de los fármacos , Persona de Mediana Edad , Pronóstico , Próstata/efectos de los fármacos , Próstata/patología , Próstata/cirugía , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate structural changes in the tumor and nontumor tissues of the prostate in patients with its cancer (PC) after treatment with high-intensity focused ultrasound (HIFU) in combination with androgen deprivation to clarify criteria for evaluating the efficiency of treatment. SUBJECT AND METHODS: Comparative morphological, immunohistochemical, and morphometric analyses were carried out to examine 253 pre- and postoperative biopsy specimens, as well as transurethral resection specimens from 32 patients with localized PC and with or without a local recurrence within 3 years after a HIFU session. RESULTS: HIFU ablation was accompanied by coagulation necrosis and progressive pancreatic fibrosis with complete tumor regression or by a reduction in the number of positive columns (by an average of 58%) in cases with recurrence. An inverse relationship was found between the degree of a reduction in the nontumor parenchyma in the control specimens and the probability of a recurrence - a less than 20% reduction in the non-tumor glands corresponded to a 3.4-fold increased risk of tumor progression. The development of recurrence was associated with less differentiated PC (GS ≥4+3) and the presence of cribriform structures in the pretreatment samples. Combined androgen deprivation as the maximum blockade was associated with the most pronounced signs of therapeutic pathomorphism, with a reduction of the microcirculatory bed in the focus of residual tumor, and a decrease in the frequency of local progression. CONCLUSION: Neoadjuvant hormone therapy contributes to the enhanced efficiency of HIFU treatment for PC. A less than 20% reduction in nontumor parenchyma volumes in the control biopsy specimens may indicate insufficient ablation in pancreatic tissue and serve as a marker for increased risk of local progression.
Asunto(s)
Adenocarcinoma , Antagonistas de Andrógenos , Neoplasias de la Próstata , Ultrasonido Enfocado Transrectal de Alta Intensidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Antagonistas de Andrógenos/uso terapéutico , Humanos , Masculino , Microcirculación , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Resultado del TratamientoRESUMEN
Clinical and morphological investigation of myelofibrosis was performed in patients with chronic myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia by analyzing the morphometric parameters of trepan-biopsy material. The correlation between changes in the parameters of erythron system and distribution of myelofibrosis were analyzed. In patients with chronic myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia, the maximum suppression of the erythron was observed against the background of severe myelofibrosis. The degree of erythron inhibition correlated with distribution of the fibrous tissue in the bone marrow. In patients with onset of chronic phase of chronic myeloid leukemia and active phase of multiple myeloma, the total number of erythroid cells was lower than in active phase of chronic lymphocytic leukemia irrespective of the degree of myelofibrosis. Erythrocyte count and hemoglobin content in the peripheral blood were lower in patients with multiple myeloma and chronic lymphocytic leukemia in comparison with the corresponding parameters in patients with chronic myeloid leukemia irrespective of the severity of myelofibrosis.
Asunto(s)
Células Eritroides/patología , Eritropoyesis/genética , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Mieloma Múltiple/patología , Mielofibrosis Primaria/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Estudios de Casos y Controles , Recuento de Eritrocitos , Células Eritroides/efectos de los fármacos , Células Eritroides/metabolismo , Eritropoyesis/efectos de los fármacos , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Hemoglobinas/metabolismo , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/metabolismo , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/metabolismoRESUMEN
The expression of molecular markers characterizing activity of the tumor process and metastases (proliferation marker Ki-67, angiogenesis marker CD34, and lymphangiogenesis markers podoplanin and LYVE-1) was assessed by immunohictochemical method in the primary tumor specimens collected during surgery for cutaneous melanoma (40 patients). Proliferative activity of the tumor tissue and volume density of peritumoral blood and lymph vessels increased with increasing tumor malignancy, which could indicate the risk of metastases.
Asunto(s)
Linfangiogénesis/fisiología , Melanoma/metabolismo , Neovascularización Patológica/metabolismo , Neoplasias Cutáneas/metabolismo , Adulto , Antígenos CD34/metabolismo , Proliferación Celular/fisiología , Femenino , Humanos , Inmunohistoquímica , Técnicas In Vitro , Antígeno Ki-67/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Melanoma Cutáneo MalignoRESUMEN
Clinical-morphological study of myelofibrosis was carried out in patients with chronic lymphocytic leukemia at the debut of the disease. Trephinobiopsy specimens of the ileac bone, aspirated specimens of the bone marrow, and peripheral blood smears were studied in 80 patients. Chronic lymphocytic leukemia was associated with myelofibrosis of different severity in 22.5% cases. Morphometric analysis of trephinobiopsy specimens showed that the severity (histology and dissemination) of myelofibrosis correlated with the type of tumor involvement of the bone marrow. Focal tumor involvement of the bone marrow predominated in trephinobiopsy specimens from patients without myelofibrosis, while patients with myelofibrosis developed mainly diffuse tumor infiltration, associated with the greatest dissemination of the initial and manifest myelofibrosis. No myelofibrosis was found in patients with interstitial tumor involvement of the bone marrow. The severity of the initial and manifest myelofibrosis directly correlated with the tumor involvement of the bone marrow and peripheral blood. Evaluation of the prognosis showed that initial myelofibrosis was associated with disease standing of 5.5 months, while manifest condition with a disease of 8.5 months and longer.
Asunto(s)
Médula Ósea/patología , Leucemia Linfoide/patología , Mielofibrosis Primaria/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Morphometric study of the erythroid stem was performed in aggressive and indolent non-Hodgkin's lymphomas vs. other cells and tissues of the bone marrow (including the tumor tissue) before chemotherapy. Hypoplasia and abnormal maturation of the erythroid stem were particularly pronounced in diffuse infiltration of the bone marrow, which did not depend on lymphoma aggressiveness. Hypoplasia of the erythroid stem was often observed during focal infiltration of the bone marrow with lymphoma cells (despite a smaller area of tumor tissue in aggressive lymphomas than in indolent lymphomas). A decrease in the relative area of adipose tissue, smooth resorption of bone tissue, and myelofibrosis are the major changes in the bone marrow microenvironment.
Asunto(s)
Médula Ósea/patología , Linfoma no Hodgkin/patología , Adulto , Anciano , Biopsia , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana EdadRESUMEN
Structural changes in cells of the central compartment of the erythron depended on tumor infiltration of the bone marrow. Cytostatic therapy was shown to improve quantitative indexes, but had no effect on morphological characteristics of the erythron. Examination of trepanobiopsy specimens from the iliac crest during chemotherapy revealed the existence of specific relationships between the erythron, other cells and tissues of the bone marrow, and tumor. Significant changes in the erythron were found during diffuse tumor infiltration and treatment with anthracycline antibiotics.