23例儿童霍奇金淋巴瘤临床分析

目的：分析儿童青少年霍奇金淋巴瘤（HL）患者的病理特征、临床表现及其预后影响因素。方法：收集青岛大学医学院附属医院血液儿科2001年5年至2013年8月收治的23例经病理确诊的儿童青少年HL患者的临床资料,采用Fisher确切概率法等进行各组间差异检验。结果：确诊病例共23例,中位年龄7.5岁,男：女发病比例=6.7：1,Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期分别占13.0%、26.2%、30.4%、30.4%;结节性淋巴细胞为主型（NLPHL）1例（4.3%）,经典型HL22例（95.7%）：混合细胞型（MC）10例（43.5%）,淋巴细胞为主型（LP）11例（47.9%）,结节硬化型（NS）1例（4.3%）;受累部位以颈部淋巴结最多见,其次依次为纵隔、腹腔及腹膜后、脾、骨骼、肺组织等,其中巨大纵隔肿块者2例;具有B症状者8例（34.7%）。化疗2个疗程评估总有效率为100%,完全缓解（CR）率69.6%,部分缓解（PR）率30.4%。Ⅰ期和Ⅱ期患者CR率100%,明显高于Ⅲ期和Ⅳ期患者（50%）,P〈0.05;23例患者7例复发,复发率Ⅲ期和Ⅳ期患者为46.2%,Ⅰ期和Ⅱ期患者为11.1%,前者高于后者（P=0.0098）;有B症状与无B症状患者之间复发率有显著统计学差异（P=0.019）;2例有巨大包块患者皆复发;各病理分型与疾病的复发间差异无统计学意义（x2=2.695,P〉0.05）。结论：儿童霍奇金淋巴瘤预后相对较好,但Ⅲ期和Ⅳ期、合并B症状及大肿块或大纵隔肿瘤的患者复发率高,应依据疾病危险度分层治疗,以期更好的预后。     

A clinicopathological study of non-Hodgkin's malignant lymphomas in terms of the Kiel classification.

A group of 25 patients with non-Hodgkin's lymphoma was investigated. Patients diagnosed earlier were reclassified according to the Kiel system. A correlation between age distribution and histological malignancy was found. The time between the onset of symptoms and diagnosis was 1 year on an average. The majority of the patients belonged to stage IV. The survival rate was higher in the low-grade malignancy group than in the high-grade group. When assessing the prognosis, the histological classification as well as the clinical staging ought to be considered. The bone marrow was the most frequent extranodal site of involvement in stage IV. Cytopenic changes were almost invariably accompanied by bone marrow infiltration. All the 7 cases analysed for lymphocyte surface markers proved to be B cell type. No significant difference was seen between the results of single agent and combined chemotherapy.     

Juvenile malignant lymphomas. 2 Non-Hodgkin lymphomas

Between 1970 and 1978 33 children with Non-Hodgkin-lymphomas at the age of 2-15 years were treated at the university children's hospital of Jena. 27 patients showed the first appearance of the disease, 6 patients had already been treated in other hospitals and were admitted with relapses. The biopsy material was classified or re-classified after the Kiel-classification. Beside the histological classification the surface markers of the malignant cells of NHL-patients were determined. 20 of 33 children were already in stage IV (Ann-Arbor-classification). Among our patients were 6 lymphoblastic NHL of Brukitt type, 10 of the convoluted cell type and 16 unclassified and one lymphoblastic lymphoma. The main localization of the NHL were mediastinum [15] and the gastrointestinal tract [10]. The therapy consisted of irradiation and chemotherapy (2 protocols) and, in case of an abdominal localization, in the attempt at a radical operation. Patients of stage I and stage II showed a complete remission rate of 50 per cent for 3 years; patients of stages III and IV of 20 per cent only. NHL of the convoluted cell type and of the Burkitt-type proved to have worse three-year-remission rates (16 per cent and 27 per cent) than unclassified lymphoblastic NHL (42 per cent).     

Serum lactate dehydrogenase isoenzyme pattern in non-Hodgkin's lymphomas

Serum lactate dehydrogenase (S-LDH) and its isoenzyme pattern were assayed in 63 non-Hodgkin's lymphoma (NHL) patients, 37 at diagnosis, 15 at relapse and 11 in complete remission (CR). S-LDH in NHL patients with active disease was higher than in normal subjects and CR patients (p less than 0.001). Among the isoenzymes, LDH-2 and LDH-5 showed no remarked differences; LDH-1 was reduced and LDH-3 and LDH-4 raised in comparison to the normal group (p less than 0.001). S-LDH levels and isoenzymes 1 and 4 were influenced by the stage, the histological subgroup and by the presence of general symptoms. In fact, cases in stage IV, with "high-grade malignancy" and with general symptoms, had higher S-LDH levels and more evident LDH-1 and LDH-4 changes than the other stages, the other histopathological subgroups and the cases classified as "A". S-LDH was the same as in normal subjects in the "low-grade" and "intermediate-grade" malignancies as was LDH-1 in stage II and LDH-4 in stages II and III, in "low-grade" malignancy and in the A cases. In contrast, LDH-3 was always high, with no significant difference in relation to the variables considered. Thus, in NHL, LDH-3 seems to be a reliable marker of the presence of the disease in any case, whereas S-LDH is more related to the spread of the lymphoma.     

Downregulation of exosome-encapsulated miR-548c-5p is associated with poor prognosis in colorectal cancer

The role of circulating exosomal microRNAs (miRNAs) in colorectal cancer (CRC) has drawn more and more attention during the past few years. Previously, we have identified several specific miRNAs in serum exosomes as potential CRC biomarkers. However, little is known about the association between exosome-encapsulated miR-548c-5p and outcomes of patients with CRC. In the current study, the expression of serum exosomal miR-548c-5p was investigated by quantitative real-time polymerase chain reaction. Its correlation with CRC prognosis was estimated by Kaplan-Meier survival and log-rank tests. Cox regression analysis based on uni- and multivariate analyses was performed to estimate the relationship of exosome-encapsulated miR-548c-5p with the clinicopathological factors of patients with CRC. Reduced levels of serum exosomal miR-548c-5p were more significant in CRC patients with liver metastasis and at later TNM stage (III/IV tumor stages). Serum exosomal miR-548c-5p could inhibit the proliferation of CRC cells, while the precise molecular mechanisms warranted further elucidation. In addition, decreased levels of serum exosomal miR-548c-5p were independently associated with shorter overall survival in CRC adjusted by age, sex, tumor grade vascular infiltration, TNM stage (III/IV tumor stages) and metastasis (hazard ratio = 3.40, 95% confidence interval 1.02-11.27; P = 0.046). The downregulation of exosomal miR-548c-5p in serum predicts poor prognosis in patients with CRC. Exosomal miR-548c-5p may be a critical biomarker for CRC diagnosis and prognosis.     

Clinical Features,Treatment and Outcome of Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Ocular Adnexa: Single Center Experience of 60 Patients

Background

Orbital marginal zone B-cell lymphoma (OAML) constitutes for the most frequent diagnosis in orbital lymphoma. Relatively little data, however, have been reported in larger cohorts of patients staged in a uniform way and no therapy standard exists to date.

Material and Methods

We have retrospectively analyzed 60 patients diagnosed and treated at our institution 1999–2012. Median age at diagnosis was 64 years (IQR 51–75) and follow-up time 43 months (IQR 16–92). All patients had undergone uniform extensive staging and histological diagnosis was made by a reference pathologist according to the WHO classification.

Results

The majority of patients presented with stage IE (n = 40/60, 67%), three had IIE/IIIE and the remaining 17 stage IVE. Seven patients with IVE had bilateral orbital disease whereas the others showed involvement of further organs. Treatment data were available in 58 patients. Local treatment with radiotherapy (14/58, 24%) or surgery (3/58, 5%) resulted in response in 82% of patients. A total of 26 patients (45%) received systemic treatment with a response rate of 85%. Nine patients received antibiotics as initial therapy; response rate was 38%. Watchful-waiting was the initial approach in 6/58 patients. In total 28/58 patients (48%) progressed and were given further therapy. Median time-to-progression in this cohort was 20 months (IQR 9–39). There was no difference in time-to-progression after first-line therapy between the different therapy arms (p = 0.14). Elevated beta-2-microglobulin, plasmacytic differentiation, autoimmune disorder and site of lymphoma were not associated with a higher risk for progress.

Conclusion

Our data underscore the excellent prognosis of OAML irrespective of initial therapy, as there was no significant difference in time-to-progression and response between local or systemic therapy. In the absence of randomized trials, the least toxic individual approach should be chosen for OAML.     

Combination v. sequential therapy with melphalan, 5-fluorouracil and methotrexate for advanced ovarian cancer.

The results of a national clinical trial to compare combination and sequential chemotherapy for stage III or IV ovarian cancer are reported. Of the 253 patients from 16 centres across Canada who were admitted to the trial 13 were excluded from the analysis. All the patients were observed for 2 to 5 years from entry into the trial. There were no differences in response to therapy or in survival between the patients treated with melphalan followed by 5-fluorouracil and then by methotrexate in high dosage and the patients treated with the same agents in combination. Patients with minimal residual disease after resection of stage III ovarian cancer had a good prognosis. Other favourable prognostic factors were age (less than 55 years), performance status (90% or 100% on the Karnofsky scale) and histologic grade of the tumour.     

Primary malignant lymphoma cutis.

Between 1934 and 1975, 16 patients with primary malignant lymphoma cutis were seen at the Ottawa clinic of the Ontario Cancer Foundation. The lesions were purplish, firm, dermal or hypodermal (or both) nodules, tumours and plaques. In all 16 the histopathologic diagnosis was diffuse non-Hodgkin''s lymphoma; 12 were considered to have prognostically bad lymphomas. However, the prognosis of primary malignant lymphoma cutis is significantly more favourable than is implied by the stage IV designation that such localized extranodal involvement would have required under the Rye clinical staging classification.     

Prognostic value of non-MHC-restricted killer cell activity in lung cancer

The prognostic value of peripheral blood non-MHC-restricted cytotoxicity against the myeloid leukaemic line K562 in lung cancer patients was studied. At the time of diagnosis and before operation, 57 patients with lung cancer were tested for cytotoxicity and subsequently followed for up to 4 years. In addition, 145 lung cancer patients, 30 patients with non-neoplastic lung diseases and 76 healthy donors were tested for cytotoxicity without the follow-up, in order to correlate the stage of lung cancer and the growth rate of tumours to the level of non-MHC-restricted cytotoxicity. On average, lung cancer patients had similar non-MHC-restricted cytotoxicity to the controls. However, patients with stage II–IV diseases showed an impaired activity, stages III and IV differing significantly from the controls. This result shows that the decline in natural killer (NK) activity is associated with tumour burden. Patients with slowly growing neoplasms had stronger cytotoxic activity than patients with fast or moderately progressing disease. In the follow-up study, the whole material of 57 patients showed only a slight correlation between cytotoxicity and survival: 42% of the patients with strong activity survived for more than 2.5 years, whereas 6% of the patients with weak activity did so. In stage I patients there was no correlation between cytotoxicity and survival, nor was there a correlation in patients with stages II–IV of the disease. Hence, in our group of patients the determination of cytotoxicity preoperatively yielded no prognostic information beyound that already available from staging. However, those stage II–IV patients that survived for 1 year or more after the diagnosis and cytotoxicity tests, showed a significant correlation between cytotoxicity and survival.     

Outcome of [131I]metaiodobenzylguanidine therapy of neuroblastoma: seven years after.

Beginning in 1984 and based on a total of 40 treatments with [131I]metaiodobenzylguanidine (131I-MIBG) in most cases with a follow-up of 5 years or more, it seems to be worthwhile reevaluating our clinical data and draw some final conclusions: We treated 12 children with a neuroblastoma (NB) IV and 3 with a NB III. In no case 131I-MIBG was the primary therapy. The great majority suffered from recurrence. The mean treatment interval after chemotherapy was 6 months (range 0-54). We calculated a median cumulative tumor dose of 77 Gy (range 0-259) in patients with stage III and 30 Gy (range 4-267) in stage IV NB. The tumor half-life time of 131I-MIBG does not significantly differ between stage III (3 days) and IV (2-5 days). Although the median tumor dose of stage III NB exceeded that of stage IV, we found in NB IV a significant tumor remission in 7 out of 12 cases. On the other hand, a slight reduction of tumor size was seen in only 1 case of stage III NB. This indicates a lower radiation sensitivity of stage III NB. Despite this fact, the two patients with stage III NB who presented a sufficient 131I-MIBG-tumor uptake turned to become operable after 131I-MIBG. Stage IV patients improved, too, even if most of them suffered from recurrence with a very poor prognosis: 3 patients of stage IV lived longer than 48-60 month or are still alive. However, no one of this group remitted completely.(ABSTRACT TRUNCATED AT 250 WORDS)     

血清Trx1、FGL2与急性心肌梗死后心力衰竭患者预后的关系

摘要 目的：探讨血清硫氧还蛋白1（Trx1）、纤维蛋白原样蛋白2（FGL2）与急性心肌梗死后心力衰竭患者预后的关系。方法：选择2019年10月至2020年5月我院收治的158例急性心肌梗死后心力衰竭患者作为观察组,并根据心功能Killip分级分为Ⅱ级组54例、Ⅲ级组57例、Ⅳ级组47例。另选择同期我院收治的102例急性心肌梗死患者作为对照组。入院后采用酶联免疫吸附法（ELISA）检测所有患者血清Trx1、FGL2水平;观察组患者出院后随访2年,并根据是否出现主要不良心血管事件（MACE）将患者分为预后不良组和预后良好组。采用多因素Logistic回归分析影响急性心肌梗死后心力衰竭患者预后的相关因素,采用受试者工作特征（ROC）曲线评估血清Trx1、FGL2对急性心肌梗死后心力衰竭患者预后的预测价值。结果：观察组血清FGL2水平明显高于对照组,血清Trx1水平明显低于对照组（P<0.05）;心功能Killip分级Ⅳ级组患者血清Trx1水平明显低于Ⅱ级组、Ⅲ级组（P<0.05）,血清FGL2水平明显高于Ⅱ级组、Ⅲ级组（P<0.05）。预后不良组患者血清Trx1、LVEF均明显低于预后良好组,而年龄、血清FGL2及血尿酸、血肌酐、N末端B型利钠肽原（NT-proBNP）均明显高于预后良好组（P<0.05）,两组心功能Killip分级比例比较差异有统计学意义（P<0.05）。多因素Logistic回归分析显示,年龄（较高）、心功能Killip分级为Ⅳ级、Trx1下降、FGL2升高均是影响急性心肌梗死后心力衰竭患者预后的危险因素（P<0.05）。ROC曲线结果显示,血清Trx1、FGL2预测急性心肌梗死后心力衰竭患者预后的曲线下面积分别为0.807、0.811,两者联合检测预测急性心肌梗死后心力衰竭患者预后的曲线下面积为0.889。结论：急性心肌梗死后心力衰竭患者血清中Trx1水平降低,FGL2水平升高,且血清Trx1、FGL2水平与患者心功能分级及预后密切相关,可作为评估急性心肌梗死后心力衰竭患者预后的辅助性指标。     

Angiocentric T-cell lymphoma

SUMMARY: The CD20+ variant of angiocentric T-cell lymphoma is an unusual type of T-cell lymphomas that present cystic changes in organs because of ischaemic necroses. The purpose of this study was to describe a case of CD20+angiocentric T-cell lymphoma, discussing its clinical, histopathological and immunohistochemical features, to analyze its proliferation kinetics and to consider its possible relationship to the Epstein-Barr virus (EBV) to understand better the pathobiological nature of the disease. METHODS: The clinical, histopathological, immunohistochemical and single-cell DNA cytophotometric features of the case were analyzed. In addition in situ hybridization was performed to detect EBV. RESULTS: The 24 years old woman was admitted to our Institute because of pain in the abdominal region and weight loss. There were enlarged lymph nodes on the neck, and biopsy was done. Histological diagnosis: angiocentric T-cell lymphoma, CD20+ variant. CD3, CD43, CD45RA and CD45R0 antigens were positive in the atypic lymphoid cells of the tumour and in cells infiltrating the vascular wall. DNA index was 0.8589 (hypodiploid). Tumour cells in G1 phase: 47%, S phase: 45.4%, G2 phase: 7.6%. Combined chemotherapy was administered because of clinical stadium IV/B of malignant lymphoma (5 CHOP-Bleo, CEPP, CEP, CMVE treatment). The disease showed gradual progression and the patient died 14 months after the first symptoms had appeared. CONCLUSIONS: In the last 13 years there were 5 cases of angiocentric T-cell lymphoma at our Institute. The CD20+ variant is rare, its clinical symptoms are special, the prognosis is unfavourable. The cause why we demonstrate this case is to call attention to a new treatment for these patients by immunotherapy using monoclonal antibodies against CD20 antigen.     

Concepts and terminology of apical dominance

Apical dominance is the control exerted by the shoot apex over lateral bud outgrowth. The concepts and terminology associated with apical dominance as used by various plant scientists sometimes differ, which may lead to significant misconceptions. Apical dominance and its release may be divided into four developmental stages: (I) lateral bud formation, (II) imposition of inhibition on lateral bud growth, (III) release of apical dominance following decapitation, and (IV) branch shoot development. Particular emphasis is given to discriminating between Stage III, which is accompanied by initial bud outgrowth during the first few hours of release and may be promoted by cytokinin and inhibited by auxin, and Stage IV, which is accompanied by subsequent bud outgrowth occurring days or weeks after decapitation and which may be promoted by auxin and gibberellin. The importance of not interpreting data measured in Stage IV on the basis of conditions and processes occurring in Stage III is discussed as well as the correlation between degree of branching and endogenous auxin content, branching mutants, the quantification of apical dominance in various species (including Arabidopsis ), and apical control in trees.     

Gallbladder carcinoma: a retrospective analysis of twenty-two years experience of a single teaching hospital

BACKGROUND: The purpose of this study was to retrospectively evaluate our experience with gallbladder cancer since the establishment of a tumour registry in our institute. METHODS: Between 1975 and 1998, 23 consecutive patients with gallbladder cancer were identified using the tumour registry database. There were 18 females (78%) and 5 (22%) males. The mean age at diagnosis was 70.6 (range 42-85) years. The diagnosis was achieved either intra-operatively or following the histological analysis of the gallbladder (n = 17), following gallbladder or liver biopsy (n = 4) or at autopsy (n = 2). Presenting symptoms included upper abdominal pain, weight loss, nausea, vomiting, fever, painless jaundice, hepatomegaly, upper abdominal mass, upper abdominal tenderness, and gastrointestinal haemorrhage. RESULTS: Histological examination revealed 20 adenocarcinomas (87%), 2 squamous cell carcinomas (9%) and one spindle cell sarcoma (4%). At presentation, 14 (61%) gallbladder cancers were stage IV, 5 (22%) were stage III and 4 (17%) were stage II. Kaplan Meier analysis revealed a mean survival of 3.2, 7.8 and 8.2 months for stage IV, III, and II disease respectively. Out of 14 patients with stage IV disease, 8 patients received adjuvant chemotherapy and survived for 4.6 months whereas six patients who did not receive adjuvant chemotherapy survived for 1.3 months. This difference was statistically significant (p = 0.04). CONCLUSION: The majority of patients with gallbladder cancer presented with advanced stage disease (stage IV) which carries a dismal prognosis. Patients who received chemotherapy with stage IV disease, however, did better than those who did not, but this is probably a reflection of patient selection.     

氟达拉滨联合化疗方案对复发性非霍奇金淋巴瘤的疗效研究

目的：探讨氟达拉滨为主联合化疗方案对复发性非霍奇金淋巴瘤的临床疗效。方法：用氟达拉滨为主的方案（FMD）化疗复发性非霍奇金淋巴瘤17例,以EPOCH方案化疗14例患者,比较两组疗效。结果：FMD方案化疗有效率为70．6％,高于EPOCH方案的50．0％,但是差异无统计学意义（P〉0．05）。FMD化疗方案在对低度恶性组疗效最佳,优于高度恶性组和中度恶性组（P〈0．05）;对不同临床分期（I、II、III、Ⅳ期）患者和不同免疫细胞分型患者,其有效率无统计学差异（P〉0．05）。在各种不良反应中,FMD组白细胞减少率、转氨酶升高率低于EPOCH组（P〈0．05）。结论：以氟达拉滨为主联合化疗方案对复发性非霍奇金淋巴瘤的临床疗效好,毒副反应轻,预后良好。     

Decadent sporulation mutants of Bacillus subtilis.

In decadent sporulation mutants, sporulating populations are heterogeneous: the cells reach successive chemical and physical resistances with progressively decreasing frequencies. Each decadent mutant can be characterized by the shape and slope of the curve describing the frequency of cells resistant to various agents ('the resistance spectrum'). In some mutants the resistance spectrum decreases progressively from xylene resistance to heat resistance; in other mutants it decreases rapidly between octanol resistance and chloroform resistance. Electron microscopy showed that in two mutants the majority of the cells are blocked at stages III and IV; the number of cells that develop further to reach successive morphological stages falls off progressively. In two other mutants most cells reach stage V. Cortexless spores are also frequent. One of the decadent mutations, SpoL1, was localized between aroD and acf. The phenotype of decadent mutants is discussed in terms of sequential gene activation.     

慢性心力衰竭患者血清Galectin-3、hs-cTnT、Cys C和PTX-3水平变化及临床意义

目的:研究慢性心力衰竭(CHF)患者血清半乳糖凝聚素-3(Galectin-3)、高敏肌钙蛋白-T(hs-cTnT)、胱抑素C(Cys C)和正五聚体蛋白-3(PTX-3)水平变化及临床意义。方法:选择2017年2月～2018年6月我院收治的CHF患者100例,按照美国心脏病协会(NYHA)心功能分级标准将其分成NYHAⅡ级组39例、NYHAⅢ级组33例、NYHAⅣ级组28例,根据随访1年患者预后情况将主要心脏不良事件患者记作预后不良组(n=27),其余记为预后优良组(n=73),另取同期于我院进行体检的健康者30例作为对照组。分别比较CHF患者和对照组的心功能指标、血清Galectin-3、hs-cTnT、Cys C、PTX-3水平,分析CHF患者上述指标的相关性及其与CHF预后情况的关系。结果:对照组、NYHAⅡ级组、NYHAⅢ级组、NYHAⅣ级组左心室舒张末期内径(LVEDD)呈逐渐增大趋势,而左心室射血分数(LVEF)呈逐渐降低趋势(P0.05)。对照组、NYHAⅡ级组、NYHAⅢ级组、NYHAⅣ级组血清Galectin-3、hs-cTnT、Cys C和PTX-3水平呈逐渐升高趋势(P0.05)。经Pearson相关性分析可得:CHF患者LVEDD与血清Galectin-3、hs-cTnT、Cys C、PTX-3水平呈正相关关系,而LVEF与血清Galectin-3、hs-cTnT、Cys C、PTX-3水平呈负相关关系(P0.05)。CHF预后优良组血清Galectin-3、hs-cTnT、Cys C、PTX-3水平均低于预后不良组(P0.05)。结论:CHF血清Galectin-3、hs-cTnT、Cys C和PTX-3水平均呈明显高表达,且与患者的病情严重程度呈密切相关,临床上可通过检测上述指标水平,继而为CHF临床诊断、预后评估提供参考依据。     

Age differences in presentation,diagnosis pathway and management of colorectal cancer

BackgroundThe gap in survival between older and younger European cancer patients is getting wider. It is possible that cancer in the elderly is being managed or treated differently than in their younger counterparts. This study aims to explore age disparities with respect to the clinical characteristics of the tumour, diagnostic pathway and treatment of colorectal cancer patients.MethodsWe conducted a multicenter cross sectional study in 5 Spanish regions. Consecutive incident cases of CRC were identified from pathology services. Measurements: From patient interviews, hospital and primary care clinical records, we collected data on symptoms, stage, doctors investigations, time duration to diagnosis/treatment, quality of care and treatment.Results777 symptomatic cases, 154 were older than 80 years. Stage was similar by age group. General symptoms were more frequent in the eldest and abdominal symptoms in the youngest. No differences were found regarding perception of symptom seriousness and symptom disclosure between age groups as no longer duration to diagnosis or treatment was observed in the oldest groups. In primary care, only ultrasound is more frequently ordered in those <65 years. Those >80 years had a significantly higher proportion of iron testing and abdominal XR requested in hospital. We observed a high resection rate independently of age but less adjuvant chemotherapy in Stage III colon cancer, and of radiotherapy in stage II and III rectal cancer as age increases.ConclusionThere are no relevant age disparities in the CRC diagnosis process with similar stage, duration to diagnosis, investigations and surgery. However, further improvements have to be made with respect to adjuvant therapy.     

Long non-coding RNA as a novel biomarker and therapeutic target in aggressive B-cell non-Hodgkin lymphoma: A systematic review

Cancer initiation and progression have been associated with dysregulated long non-coding RNA (lncRNA) expression. However, the lncRNA expression profile in aggressive B-cell non-Hodgkin lymphoma (NHL) has not been comprehensively characterized. This systematic review aims to evaluate the role of lncRNAs as a biomarker to investigate their future potential in the diagnosis, real-time measurement of response to therapy and prognosis in aggressive B-cell NHL. We searched PubMed, Web of Science, Embase and Scopus databases using the keywords “long non-coding RNA”, “Diffuse large B-cell lymphoma”, “Burkitt's lymphoma” and “Mantle cell lymphoma”. We included studies on human subjects that measured the level of lncRNAs in samples from patients with aggressive B-cell NHL. We screened 608 papers, and 51 papers were included. The most studied aggressive B-cell NHL was diffuse large B-cell lymphoma (DLBCL). At least 79 lncRNAs were involved in the pathogenesis of aggressive B-cell NHL. Targeting lncRNAs could affect cell proliferation, viability, apoptosis, migration and invasion in aggressive B-cell NHL cell lines. Dysregulation of lncRNAs had prognostic (e.g. overall survival) and diagnostic values in patients with DLBCL, Burkitt's lymphoma (BL), or mantle cell lymphoma (MCL). Furthermore, dysregulation of lncRNAs was associated with response to treatments, such as CHOP-like chemotherapy regimens, in these patients. LncRNAs could be promising biomarkers for the diagnosis, prognosis and response to therapy in patients with aggressive B-cell NHL. Additionally, lncRNAs could be potential therapeutic targets for patients with aggressive B-cell NHL like DLBCL, MCL or BL.     

Diagnosis delay in Libyan female breast cancer

ABSTRACT: BACKGROUND: To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya METHODS: 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008--2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time) was categorized into 3 periods: <3 months, 3--6 months, and >6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay). Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire) during an interview with each patient and from medical records. RESULTS: The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3--6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer) was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s) that did not include a lump (p < 0.0001), with women who did not report monthly self examination (p < 0.0001), with old age (p = 0.004), with illiteracy (p = 0.009), with history of benign fibrocystic disease (p = 0.029) and with women who had used oral contraceptive pills longer than 5 years (p = 0.043). At the time of diagnosis, the clinical stage distribution was as follows: 9.0% stage I, 25.5% stage II, 54.0% stage III and 11.5% stage IV.Diagnosis delay was associated with bigger tumour size (p <0.0001), with positive lymph nodes (N2, N3; p < 0.0001), with high incidence of late clinical stages (p < 0.0001), and with metastatic disease (p < 0.0001). CONCLUSIONS: Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast cancer. Especially, guidelines for good practices in managing detectable of tumors are necessary.