Establishment of patient derived xenograft model of high-grade mucinous carcinoma peritonei accompanied with signet ring cells and identification of biological characteristics / 中华肿瘤杂志

Objective@#To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP.@*Methods@#PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded.@*Results@#The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%.@*Conclusion@#PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

Correlation studies of ultrasonic morphological types and the biological variation in calcification of the differentiated thyroid cancer / 中华超声影像学杂志

Objective@#To explore the correlation between ultrasound features and tumor biological variation with calcification morphological types in differentiated thyroid carcinoma (DTC).@*Methods@#The clinical data of 598 patients with DTC calcification diagnosed by ultrasound, surgery and clinicopathology were retrospectively analyzed. According to the 2017 edition of the American College of Radiology (ACR) Thyroid Imaging Report and Data System (TI-RADS) classification system standard, DTC ultrasonic calcification morphological characteristics were divided into 5 types, and the correlation between DTC ultrasonic calcification morphological types and tumor biological characteristics and their variations were analyzed by Spearman correlation analysis.@*Results@#Of the 598 patients, 527 cases (88.13%) were typical papillary thyroid cancer(PTC), 27 cases (4.52%) were typical follicular thyroid cancer(FTC), and 44 cases (7.36%) were variant subtype (including 25 cases of follicular type, 9 cases of high cell type, 6 cases of clear cell type and 4 cases of eosinophilic type). TI-RADS diagnosis: 44 cases (7.36%) were Ⅰ~Ⅲ class, 179 cases (29.93%) were Ⅳ class performing fine needle aspiration cytology(FNAC), 375 cases (62.71%) were Ⅴ class. The coincidence rate between ultrasound and clinicopathological diagnosis was 92.64% (554/598). Morphological types of ultrasonic calcification in 554 cases of DTC: type Ⅰ microcalcification in 416 cases (75.09%); type Ⅱ calcification in 71 cases (12.82%); type Ⅲ calcification in 41 cases (7.40%); type Ⅳ calcification in 20 cases (3.61%); type Ⅴ calcification in 6 cases (1.08%). There were correlations between type Ⅰ, Ⅱ, Ⅲ ultrasonic calcification morphological types and the tumor biological characteristics and its variant subtypes of DTC(r=0.634, 0.592, 0.479; all P=0.01).@*Conclusions@#TI-RADS Ⅳ-Ⅴ class level+ Adler Ⅱ-Ⅲ blood flow has a high practical value for the ultrasonic diagnosis of DTC, and FNAC can be performed in suspicious type Ⅳ DTC. Type Ⅰ-Ⅲ ultrasonic calcification morphological types and the main types of tumor biological characteristics and its variant of DTC, and has an important clinical value for the diagnosis of DTC by ultrasound, which provides an important reference basis for guiding FNAC, selecting surgical procedure, postoperative follow-up and prognosis judgment.

¿Tiene valor pedir más de un perfil inmunohistoquímico en tumores multicéntricos o multifocales de mama? / Has it any value to request more than one immunohistochemical profile in multicentric or multifocal breast tumors?

Introducción La estimación de la prevalencia de tumores mamarios multicéntricos y multifocales es muy variable según los distintos estudios analizados. Esto se debe, en gran parte, a la falta de consistencia al momento de definir ambas formas de presentación. Por este motivo, muchos autores hacen referencia a este tipo de tumor como carcinoma mamario múltiple. El tnm, uicc-ajcc (7ma edición) define a esta forma de presentación como múltiples lesiones de carcinoma mamario presentes en la misma mama de manera sincrónica. Según el Colegio Americano de Patólogos (cap), la caracterización biológica de la lesión de mayor tamaño tumoral es suficiente, salvo que se presenten discordancias entre los tipos histológicos o grados tumorales. A pesar de que la estrategia de evaluar una única lesión en este aspecto tiene claras ventajas en costos y viabilidad, el cáncer de mama es considerado en sí mismo una enfermedad heterogénea, y, al seguir las recomendaciones anteriormente expresadas, se estaría asumiendo que estos tipos de tumores múltiples tienen un comportamiento biológico homogéneo. Por tal motivo, en el presente estudio se analiza el comportamiento biológico (re, rp, her2 y Ki-67) en cada foco tumoral presente, para poder establecer si, al seguir las recomendaciones vigentes actualmente, no estaríamos subtratando a un grupo de nuestras pacientes. Objetivos Evaluar la concordancia en los perfiles inmunohistoquímicos de cada tumor presente de manera sincrónica en la mama. Establecer la asociación entre los tamaños, los tipos histológicos y el grado tumoral. Material y método Se realizó un estudio observacional, retrospectivo en pacientes con diagnóstico y confirmación por estudio histopatológico de pieza quirúrgica de carcinoma mamario multifocal o multicéntrico. De un total de 722 pacientes, se obtuvieron datos de 45 historias clínicas, en un período comprendido, entre marzo de 2015 y septiembre de 2016 (18 meses). Las pacientes analizadas fueron diagnosticadas y tratadas en la Unidad de Mastología de la Clínica Breast y el Hospital Italiano de la Ciudad de La Plata, Buenos Aires, Argentina. Los resultados histopatológicos e Inmunohistoquímicos (ihq) se obtuvieron de los patólogos pertenecientes a nuestro centro mastológico. El perfil ihq se realizó en tejido tumoral obtenido mediante biopsia con aguja gruesa o pieza quirúrgica. Se determinó: Receptores Hormonales para Estrógeno (re) y Progesterona (rp), her2 y Ki-67. Resultados • Se observó una incidencia de 6,23% de tumores multicéntricos, multifocales. • En cuanto al tipo histológico, la correlación entre biopsia con aguja gruesa y análisis de pieza quirúrgica fue del 100% (n:45 pacientes). • Grado histológico tumoral en los distintos focos: 84% (n=38) de concordancia y 16% (n=7) de discordancia. • Variabilidad de subtipos tumorales en cada foco: el 67% (n=30) no presentó discordancias. • Perfil inmunohistoquímico (ihq): el porcentaje de pacientes con concordancia en el perfil inmunohistoquímico y el subtipo tumoral fue superior al grupo de pacientes que presentaron discordancias. En el grupo de pacientes con discordancias, un 20% sobreexpresó el marcador her2. Conclusiones Teniendo en cuenta la heterogeneidad tanto intratumoral como entre los distintos focos que se presenta en estos tumores múltiples, es importante obtener la mayor información posible sobre la morfología y el perfil inmunohistoquímico.

Estimates of the prevalence of multicentric and multifocal breast tumors is highly variable depending on the different studies analyzed, and this is due largely to the lack of consistency when defining both forms of presentation. For this reason, many authors refer to this type of tumor as multiple breast carcinoma. The tnm (7th edition) defines this presentation as multiple lesions of breast carcinoma present in the same breast synchronously. According to the College of American Pathologists (cap), biological characterization of the lesion of the largest tumor is sufficient, unless discrepancies between the histological tumor types or degrees are presented. Although the strategy of evaluating a single lesion in this regard, has clear advantages in cost and viability, breast cancer is considered itself an heterogeneous disease, and following the recommendations previously expressed, it would be assuming that these type of multiple tumors have a homogeneous biological behavior. Therefore, in this study the biological behavior (er, pr, her2 and Ki-67) is analyzed in each tumor focus, to determine whether to follow the recommendations currently in force, we would not be sub-treatment a group of our patients.

Application of PBL combined with LBL teaching method in cancer diagnosis teaching / 中华医学教育探索杂志

Objective To determine the effects and advantage of PBL teaching method combined with LBL teaching method over LBL teaching method. Methods The interns from Department of Clinical Laboratory were selected as teaching subjects. Fifty interns were assigned randomly into two groups, 25 in PBL+LBL group, 25 in LBL group. After the designed teaching, the exam scores and satisfaction question-naire was evaluated. All the data was analyzed with SPSS 22.0. Counting data was analyzed with Chi-square, Fisher test because of smaller number. Results In the exam test, the scores in PBL+LBL teaching group were significantly higher than that in the LBL group [(84.40±5.14) vs. (78.72±6.51)]. In the questionnaires, the satisfaction rate in the PBL+LBL group was also higher than that in the LBL group. The PBL+LBL teach-ing is helpful for improving the self-learning and collabora-tion ability of the students. Conclusion PLB+LBL teaching method in tumor diagnosis showed improved teaching effects and higher satisfaction rate.

Oncogene-induced transcriptional patterns in established cell lines as a model for in vitro analysis of tumor biology

Established cell lines have long been used for in vitro studies of tumor biology, enabling investigators to control growth conditions and to draw important conclusions about the oncogenic microenvironment. However, gene expression behavior in cultured cells may not always reflect the actual in vivo scenario, and analysis derived from such experiments should take into consideration the existing differences between the two environments. We used suppression subtractive hybridization to study transcriptional changes elicited after oncogene transformation and cell line establishment. We found that transcriptional changes elicited in cultured cell lines are in fact representative of late events, and they do not occur early after oncogene transfection or activation. We also determined that a fraction of the transcriptional changes is oncogene specific, whereas other changes are shared between two or more different oncogenes.

Effects of Nitric Oxide on Growth and Metastasis of Tumor / 中国普外基础与临床杂志

Objective To study the effects of nitric oxide (NO) on the growth and metastasis of tumor.Methods The literatures of recent years were reviewed.Results NO had double effects on the growth and metastasis of tumor. NO promoted the growth and metastasis by regulating the expression of tumor proliferation gene and inducing tumor angiogenesis. On the other hand, NO had antitumor effects by interfering with the metabolism of tumor cells, inducing the damage of DNA, forming high toxic free radical, inducing apoptosis of tumor cells and mediating the antitumor action of endothelial cells and macrophages.Conclusion Selective blockage or induction of synthesis of NO may be a new way for tumor therapy.

The Impact of Patient Age upon Locoregional and Systemic Failures after Breast Conservation Therapy: Comparison of the Results from the Groups above and below 35 Years / 한국유방암학회지

PURPOSE: It has long been controversial whether breast cancer of the younger women is more aggressive than that of older women and remains unclear whether the dismal outcome seen in the younger age group is a reflection of more advanced disease at the time of diagnosis or whether it is due to a difference in the underlying tumor biology. To investigate the outcome of primary breast cancers treated with breast conservation surgery according to the patient's age, we undertook this study. METHODS: One hundred and eighty-five patients with breast carcinoma, that underwent breast conservation surgery at the Severance Hospital, Yonsei University College of Medicine, during the period between July 1988 and December 1996, were divided into two groups on the basis of age 35 (patient group: age 35 or younger, and control group: over 35 years of age). Tumor stage by the American Joint of Committee on Cancer (AJCC) classification, histologic grade, adjuvant therapy, and the incidence of local or systemic recurrences were analyzed. Finally 10-year loco-regional recurrence free, distant relapse free (DRFS) and overall survival (OS) were estimates determined by Kaplan-Meier analysis. RESULTS: Among 185 patients, 42 women (22.7%) were included in the patient young group and the other 143 in the control group. There were no significant differences between the two groups in terms of the distribution of T stages, N stages, histologic subtypes, hormonal receptor expressions, and mean follow-up duration. The younger group had higher 10-year local recurrence (14.3%) and systemic recurrence (28.6%) rates than the control group (4.2% and 12.6%), respectively (p<0.05). The younger group also had a significantly worse 10-year overall survival rate of 78.6% (p<0.01). CONCLUSION:These results indicate that breast cancer patients younger than 35 years of age have higher local and systemic recurrences and poorer DRFS and OS than their older counterparts. These differences may reflect difference in tumor biology and imply that younger patients with breast cancer need both more aggressive and adequate systemic treatment after surgery.

The Impact of Patient Age upon Locoregional and Systemic Failures after Breast Conservation Therapy: Comparison of the results from the groups above and below 35 years

PURPOSE: It has long been controversial whether breast cancer of the younger women is more aggressive than that of older women and remains unclear whether the dismal outcome seen in the younger age group is a reflection of more advanced disease at the time of diagnosis or whether it is due to a difference in the underlying tumor biology. To investigate the outcome of primary breast cancers treated with breast conservation surgery according to the patient's age, we undertook this study. METHODS: One hundred and eighty-five patients with breast carcinoma, that underwent breast conservation surgery at the Severance Hospital, Yonsei University College of Medicine, during the period between July 1988 and December 1996, were divided into two groups on the basis of age 35 (patient group: age 35 or younger, and control group: over 35 years of age). Tumor stage by the American Joint of Committee on Cancer (AJCC) classification, histologic grade, adjuvant therapy, and the incidence of local or systemic recurrences were analyzed. Finally 10-year loco-regional recurrence free, distant relapse free (DRFS) and overall survival (OS) were estimates determined by Kaplan-Meier analysis. RESULTS: Among 185 patients, 42 women (22.7%) were included in the patient young group and the other 143 in the control group. There were no significant differences between the two groups in terms of the distribution of T stages, N stages, histologic subtypes, hormonal receptorexpressions, and mean follow-up duration. The younger group had higher 10-year local recurrence (14.3%) and systemic recurrence (28.6%) rates than the control group (4.2% and 12.6%), respectively (p<0.05). The younger group also had a significantly worse 10-year overall survival rate of 78.6% (p<0.01). CONCLUSION: These results indicate that breast cancer patients younger than 35 years of age have higher local and systemic recurrences and poorer DRFS and OS than their older counterparts. These differences may reflect difference in tumor biology and imply that younger patients with breast cancer need both more aggressive and adequate systemic treatment after surgery.