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Раковая наука и терапия

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Объем 8, Проблема 4 (2016)

исследовательская статья

Therapeutic Potentials of CD151 shRNA in Targeting Metastasis of Triple Negative Breast Cancer Cell Line MDA-MB-231

Gayatri Devi V, Anil Badana, Seema Kumari, Nagaseshu P and Rama Rao Malla

Objective: CD151 is a master regulator of cell adhesion signalling and acts as a promoter in tumour progression. Induction of RNAi through shRNA expression holds great prospective in biomedical research. Bioinformatics approach used to predict potential shRNAs that knockdown CD151. The aim of present study is to investigate the role of CD151 in metastasis of triple negative breast cancer cells using shRNA. Methods: Triple negative breast cancer line, MDA-MB-231 obtained from NCCS Pune, India and expression of CD151 determined using western blot and RT-PCR analysis. Small hairpin RNA (shRNA) was constructed using pSilencer 2.1-U6 puro vector to knockdown CD151 expression. The role of CD151 in proliferation, apoptosis, migration, invasion and cell adhesion was evaluated by silencing CD151 gene using CD151shRNA.
Results: RNA interference technology (RNAi) used to silence CD151 gene expression in MDA-MB-231 cells. Delivery of specific shRNA targeting human endogenous CD151 showed significant growth inhibition of MDA- MB-231 cells. The gene expression study by RT-PCR analysis showed that expression of CD151 at mRNA level reduced six fold with CD151 gene knockdown. CD151 gene silencing for 48h using shRNA decreased proliferation by 62.7%. CD151 knockdown also lead to the significant inhibition of metastasis and induced apoptosis.
Conclusion: CD151 over expression is essential for tumour progression and our study shows that shRNA mediated gene silencing of CD151 decreases the metastasis, thus emphasizing CD151 as a prognostic marker and help in developing new therapeutics for treatment of triple negative breast cancer.

исследовательская статья

Prognostic Factors Associated with Survival in Women with Breast Cancer from Veracruz, Mexico

María Teresa Álvarez-Bañuelos, Ligia María Rosado-Alcocer, Jaime Morales-Romero, Lizbeth San Román-Álvarez, Raúl Enrique Guzmán- García and Magda Carvajal-Moreno

Objective: The present study analyzed the geographical location and prognostic, clinical, physiological, and biochemical factors associated with breast cancer (BC) in women based on their treatment.
Methods: We conducted a retrospective cohort study encompassing a 5-year follow-up period of 114 women from rural and urban areas who were diagnosed with BC in 2009 at the State Cancer Center (CECAN) in Xalapa, Veracruz, Mexico. The probability of survival was calculated using the Kaplan-Meier estimator and Log Rank test with a confidence interval of 95%. We determined the prognostic factors in a multivariate analysis using the Cox proportional hazards model. The point estimate was the hazard ratio (HR) and 95% confidence interval (CI).
Results: The overall survival ratio for the study participants was 68% and 63% after 52 and 60 months, respectively. The lowest survival ratio corresponded to clinical stages IIIB (38%) and IV (10%) and patients showing tumor cell metastasis (24%). There were significant differences between groups (p<0.001), including women under 40 years of age (36%, p<0.003) and those with positive HR (83%, p=0.006). Women who received adjuvant treatment and had a tumor size less than 2 cm lived longer (75%, p<0.001). The multivariate analysis identified a number of prognostic factors that are unfavorable for women with BC, including a diagnosis of clinical stage IV (Hazard Ratio=11.88; 95% CI=2.88-44.88) and the presence of metastasis (Hazard Ratio=4.95; 95% CI=1.78-13.76).
Conclusion: General tumor characteristics, such as metastasis, disease stage and family history, are important for survival and can serve as prognostic factors for BC patients. Moreover, the lower survival of women less than 40 years of age should be considered as a decision-making factor when selecting from treatment options.

исследовательская статья

Imaging Features, Differential Diagnosis and Management of Leiomyosarcomas: Case Series and Review of the Literature

Stramare R, Orsatti G, Attar S, Rastrelli M, Brunello A, Bortolanza C, Ortolan P and Coran A

Leiomyosarcoma (LMS) is a relatively rare malignant tumor showing smooth-muscle differentiation and accounting for 7-10% of all soft tissue tumors (STTs). LMS occurs most commonly in retroperitoneum and extremities but can potentially involve every site of the body. Diagnosis is finally provided by a histological examination; nevertheless multiplanar imaging can suggest a radiological diagnosis of soft tissue sarcoma prior to biopsy and allow a precise assessment of primary tumor extent and systemic spreading. Computerized tomography (CT) is often the first imaging modality assessment especially for abdominopelvic LMSs and also the cornerstone of staging. CT usually shows a large, heterogeneous and unspecific mass with central areas of hemorrhage or necrosis and peripheral contrast enhancement. Magnetic resonance imaging (MRI) findings are not specific and show a nonfatty mass iso-intense to skeletal muscle on T1-weighted images and high-signal in T2-weighted images with a decreasing rim-to-center pattern of enhancement after gadolinium administration. Imaging also helps in differential diagnosis that mainly concern other STT, gastrointestinal stromal tumors (GISTs), primitive neuroendocrine tumors (PNETs), and lymphomas. Prognosis of LMS is poor and patients should be referred to hospitals with extensive experience in managing sarcomas using multidisciplinary therapeutic approach including surgery, chemotherapy and radiotherapy. The aim of this review is to underline the most important radiological features that could indicate a diagnosis of LMS and in particular to draw the attention to LMSs of the limbs as one of the most frequent location even if often overlooked in literature.

История болезни

Benign Metastasizing Leiomyomas of the Lungs: A Case Report

Agnieszka Maździarz, Jolanta Kupryjańczyk and Beata Śpiewankiewicz

Background: Benign metastasizing leiomyoma (BML) is a very rare condition, which is paradoxically called benign metastases and occurs among patients with previous history of leiomyomas.
Case presentation: We report a case of a 46-year-old woman diagnosed with benign metastasizing leiomyomas of the lungs, 16 years after uterine leiomyoma removal. The patient presented with the exertion dyspnea and dry cough lasting for several weeks. CT scan was indicative of metastatic lesions in the lung and no pathological findings within the lesser pelvis and abdominal cavity. The patient underwent right video thoracoscopy followed by thoracotomy with wedge and marginal resections of the right lung tissue containing tumors. The histopathological diagnosis was: benign metastasizing leiomyomas. The patient received a single dose of Triptorelinum (Diphereline SR 3.75)-GnRH analog. Control CT performed 4, 12, 36 months later showed stabilization. The patient has been symptom-free for 5 years.
1. BML is very rare disease-no more than 100 cases have been described. Our treatment methods include: surgical resection, hormonal manipulation and observation.
2. An individual treatment strategy or observation should be consider for each patient with BML

Краткое сообщение

Combination Therapy for Chronic Lymphoid Leukemia

Satadal Barik

For decades, the treatment of chronic lymphocytic leukemia (CLL) has relied on cytotoxic drugs with incremental benefit from anti-CD20 monoclonal antibodies. However, in the past 5 years, targeted drugs have fundamentally changed the management and outcome of CLL

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