PTEN、MLL基因在T淋巴母细胞淋巴瘤/白血病的表达及其意义

Objective To investigate the significance and expression of PTEN, MLL in T lymphoblastic lymphoma/leukaemia(T-LBL/ALL). Methods Seventy-six cases of T-LBL/ALL were studied by using immunohistochemical EnVision method for PTEN. Fluorescence in-situ hybridization (FISH) for MLL gene (located on chromosome 11q23) was performed to detect its breakage and amplification. Results Among the 76 cases ofT- LBL/ALL, the positive rate of PTEN was 64.47 % (49/76), lower than that in reactivated lymphoid tissue (100 %, 20/20) (λ2= 19.220, P ＜0.05). PTEN expression was reversely correlated to theclinical stage, Ki-67 index and LDH level (P ＜0.05). Among the 76 cases, MLL gene with breakage of 11q23 was detected in 13 cases (17.11%), and amplification in 18 cases (23.68 %). Survival rate ot MLL gene breakage group was lower than that of non-breakage group (25.0 %, 43.6 %). Survival rate of MLL gene amplification group was lower than that of non-amplification group too (17.1%, 42.7 %). Both of breakage and amplification were related to prognosis ( λ 2 = 11.357, λ 2 = 4.533; P ＜0.05). Conclusion Anti-oncogene PTEN down-regulation may play an important role on the development and proceeding of T-LBL/ALL. MLL gene with breakage and amplification of 11q23 are helpful to predict prognosis of T-LBL/ALL. The case with MLL gene breakage and amplification of T-LBL/ALL may have a poor prognosis. It hints this group maybe a subtype of T-LBL/ALL.     

慢性髓性白血病衍生9号染色体ASS基因缺失与非缺失患者的临床特征

Objective To investigate the clinical characteristics of patients with chronic myeloid leukemia (CML) in chronic phase with deletion and non-deletion of the argininosuccinate synthesis gene (ASS gene) on the derivative chromosome 9. Methods The clinical data of patients with CML initially treated with imatinib and BCR/ABL1/ASS1 3-color fusion probe to detect ASS gene deletion were analyzed. The patients were divided into deletion group (n=27) and non-deletion group (n=92). Clinical characteristics, treatment effects, and prognosis were analyzed. Results The average age of 119 patients was 37.22±12.72 years old. The sokal score differed between the deletion and non-deletion groups (χ2=4.304, P=0.038). No statistically significant difference in other general characteristics was found (P>0.05). The 3-month CCyR rate, 6-month CCyR rate, and BCR-ABLIS≤1% rate in the deletion group were lower than those in the non-deletion group (P<0.05). The median follow-up of 119 patients was 35.0 (3.0-60.0) months. The PFS in the deletion group was lower than that in the non-deletion group (χ2=4.293, P=0.038). Overall survival was not significantly different between the two groups (χ2=0.008, P=0.931). Conclusion The deletion of the ASS gene in patients with chronic CML is related to the poor efficacy of imatinib treatment, poor prognosis, and high risk of disease progression. © 2023, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.     

Study on the protein expression and amplification of HER2 gene in gastric cancer

Objective： The aim of the study was to investigate the human epidermal growth factor receptor 2 （HER2） gene amplification and protein expression and interpretation points in the stomach mixed carcinomas. Methods： Immunohistochemistry （IHC） and fluorescence in situ hybridization （FISH） technique were used to detect HER2 gene amplification and expression of HER2 protein in 442 cases of gastric mixed carcinoma. Results： The expression rate of HER2 protein was 41.2% （182/442）： the HER2 protein expression IHC 3＋ extensive type in 18 cases, partial type in 21 cases, focal type in 8 cases, accounting for 10.6% （47/442）; the HER2 protein expression IHC 2＋ extensive type in 23 cases, partial type in 28 cases, focal type in 11 cases, accounting for 14.0% （62/442）; the HER2 protein expression IHC 1＋ extensive type in 27 cases, partial type in 31 cases, focal type in 15 cases, accounting for 16.5% （73/442）. HER2 gene amplification rate of 442 cases was 16.1% （71/442）. In 182 cases of HER2 protein positive expression, the HER2 gene cluster amplification rate was 14.8% （27/182）, large granular amplification rate 11.0% （20/182）, punctate amplification rate 6.0% （11/182） and high polysomy 7.1% （13/182）. In 71 cases of HER2 gene amplification, there was 42 cases of HER2 protein expression IHC 3＋, 22 cases of HER2 protein expression IHC 2＋, and 7 cases of IHC 1＋. Conclusion： HER2 detection of gastric mixed carcinoma has great heterogeneity, HER2 protein positive expression is divided into extensive type, partial type and focal type, and HER2 gene positive amplification is divided into cluster amplification, large granular amplification, punctate amplification and high polysomy. These typing of HER2 protein expression and HER2 gene amplification provide reference index to quantify for targeted therapeutic effect of anticancer drugs.     

Expression of HIF-1α and PTEN in bnman multiple myeloma bone marrow

Objective To investigate HIF-1α and PTEN expression in multiple myeloma(MM).Methods The expression of HIF-1α and PTEN was studied in 28 cases of MM with immunohistochemistry.Results Over-expression of HIF-1α was frequently(20 of 28 cases,71.4%)detected in MM bone marrow.Expression of HIF-1α between MM and control group bone marrow has significant differences(P＜0.01).The positive expression rate of PTEN in MM bone marrow was 42.9%(12 0f 28 cases).Expression of PTEN between MM and control group bone marrow has significant difierences(P＜0.01).There was negative correlation between the expression of HIF-1α protein and the PTEN protein(P＜0.05,r=-0.542).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α may play a critical role in the formation.development and invasion of MM.HIF-1α and PTEN may be used to estimate the progress of MM.     

Expression of CD44s mRNA in Gastric Carcinoma

Objective： To study the expression of CD44s mRNA in the occurrence, development and invasion of gastric carcinoma （GC）. Methods： The expressions of CD44s mRNA in 66 cases of GC, 25 cases of superficial gastritis and 25 cases of atypical hyperplasia were examined by in situ hybridization （ISH）. Results： There was no expression of CD44s mRNA in the group of superficial gastritis; the positive rate was 20%（5/25） in the group of atypical hyperplasia and 62.12%（41/66） in the group of gastric carcinoma. The positive rate in poor differentiation group was significantly higher than that in well differentiation group （P〈0.05）, and the positive rate of lymph node metastasis group was significantly higher than that in negative lymph node metastasis group（P〈0.05）. Conclusion： The expression of CD44s mRNA was related to cell differentiation degree and lymph node metastasis, the activation of CD44s gene was related to strong invasion of cancer cells and poor prognosis.     

30-bp DELETION IN LATENT MEMBRANE PROTEIN 1 （LMP-1）ONCOGENE IN LYMPHOEPITHELIAL CARCINOMA OF SALIVARY GLANDS

Objective:To investigate the 30 bp deletion in LMP-1 in lymphoepithelial carcinoma of salivary glands,and to clarify the deletion rate. Methods: 46 cases of LEC were subjected to PCR examination for the 3‘terminal region of LMP-1 gene, in order to observe the 30 bp deletion. To reduce the influence of unsuccessful DNA extraction from paraffin-embedded tissue sections,a β-actin PCR was performed at the same time.Additionally, DNA sequencing was performed on 1 case without deletion and 1 case with deletion. Results: 4 of 46 specimens were proved to contain no suitable DNA sample by β-actin gene amplification. In the remaining 42 cases, LMP-1 DNA was detected in 35/42 (83.3%)LEC cases. Two kinds of PCR products were found in these 35 cases after further DNA sequencing. 31 cases(88.6%) carried 316 bp product and 4 cases (11.4%)carried 286 bp product. Conclusion: Some LECs of salivary glands carry del-LMP-1. In our study, the deletion rate was 11.4% (4/35).     

PTEN、MLL基因在T淋巴母细胞淋巴瘤／白血病的表达及其意义

 目的　分析肿瘤抑制基因PTEN、混合系白血病（MLL）基因等在T淋巴母细胞淋巴瘤／白血病（T-LBL／ALL）的表达及意义。方法　选用76例T-LBL／ALL患者淋巴结存档蜡块,应用免疫组织化学EnVision法进行PTEN标记,用20例反应性增生淋巴结标本作正常对照。并用荧光原位杂交（FISH）技术检测MLL基因所在11q23染色体的断裂和扩增情况。结果　76例T-LBL／ALL中,PTEN的表达率为64.47 %（49／76）,低于淋巴结反应性增生的100 %（20／20）（χ2＝19.220,P＜0.05）。PTEN表达与临床分期、Ki-67、乳酸脱氢酶（LDH）呈负相关（P＜0.05）。76例T-LBL／ALL中,MLL基因发生11q23染色体断裂13例（17.11 %）,扩增18例（23.68 %）。MLL基因断裂组总体生存率（25.0 %）低于非断裂组（43.6 %）（χ2＝11.357,P＜0.05）。MLL基因扩增组总体生存率（17.1 %）低于非扩增组（42.7 %）（χ2＝4.533,P＜0.05）。结论　抑癌基因PTEN表达降低在T-LBL／ALL的发生发展中可能具有重要作用。MLL基因发生染色体11q23断裂和扩增有助于对T-LBL／ALL预后的判断,发生MLL基因断裂或扩增的T-LBL／ALL预后较差,提示MLL基因断裂或扩增可能为T-LBL／ALL的一种分子亚型。     

13号染色体、p53基因缺失与多发性骨髓瘤的相关性研究

Objective To evaluate the correlation between the del(13q14),p53 gene deletion and clinical manifestations,treatment efficacy and survival duration for multiple myeloma.Methods The clinical information and blood samples of patients with multiple myeloma were collected,and the positive rate of genetic deletion of 13q14,p53 via FISH were detected,to calculate the statistical difference between the patients with normal gene and those with genetic deletion.Results Nine of the 22 patients(40.9%)totally evaluated were detected positive for p53 gene deletion,among whom none is in Phase Ⅰ,2 cases in Phase (40.0%),and 7 in Phase Ⅲ(50.0%).Eight patients of the total patients(36.4%)were found to have del 13q14,with 3 cases in phaseⅡ(60.0%),5 cases in PhaseⅢ(35.7%)while no one in Phase Ⅰ.Four patients have the both gene mutation,and 9 patients have neither abnormal genosome.There was no difference of demographic and disease characters between genetic deletion group and the normal ones,such as ages,gender,disease type/phase,renal function,blood cell counting,LDH and serum calcium.But the myeloma cells rate is statistically higher in normal group than in the group with p53 genetic deletion[(52.25±25.4)%vs(31.1±12.9)%,P=0.043]at the first diagnosis.Five patients treated got complete remission,7 patients very good partial remission,6 patients partial remission,4 patients no response,thus the total effective rate was up to 81.8%.Four among the six patients who were treated with bertezomib reached complete remission and 1 got very good partial remission.The mean survival duration was 11 months and 47 months in p53 genetic deletion group and normal group,respectively(P=0.086),14.9 months and 43.3 months in del 13q14 group and normal ones,and 9.4 months and 45.4 months(P=0.13)in the patients with both genetic deletions and the normal groups(P=0.1 3).Conclusion There was a statistically significant relationship between the cytogenetic abnormality and the survival duration in patients with multiple myeloma.It is recommended to prescribe bortezomib to the patients with abnormal chromosome who have known to have poor prognostic and not respond to the conventional chemotherapy treatments.     

Pharmacogénétique des fluoropyrimidines. La méthylènetétrahydrofolate réductase

Résumé: Lefficacité optimale des fluoropyrimidines nécessite des concentrations élevées en 5-10 méthylènetétrahydrofolate (CH₂FH₄), contrôlées par la méthylènetétrahydrofolate réductase (MTHFR) qui convertit irréversiblement le CH₂FH₄ en 5-méthyltétrahydrofolate (CH₃FH₄). Les polymorphismes 677CT et 1298AC du gène MTHFR sont associés à une baisse dactivité de lenzyme. Les tumeurs «MTHFR mutées» devraient donc être plus sensibles aux fluoropyrimidines que les tumeurs «MTHFR sauvages». Les études expérimentales et cliniques publiées à ce jour tendent à montrer une plus grande sensibilité au 5-FU (associé ou non à lacide folinique) dans les tumeurs MTHFR mutées par rapport aux tumeurs sauvages. Ces résultats montrent la nécessité de poursuivre ces recherches afin de confirmer limpact de ces polymorphismes sur lefficacité des fluoropyrimidines.     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

PSA-Test zur Früherkennung des Prostatakarzinoms

Zusammenfassung Prostatakrebs ist hierzulande seit einigen Jahren die häufigste Krebserkrankung bei Männern. Da über die Ätiologie wenig gesichertes Wissen vorliegt und daher kaum Möglichkeiten zur primären Prävention bestehen, konzentrieren sich die Anstrengungen auf die Suche nach wirksamen Verfahren zur sekundären Prävention. Hierbei gilt die Verwendung des PSA-Tests zur Früherkennung des Prostatakarzinoms als derzeit aussichtsreichstes Verfahren. Bevor ein neues Früherkennungsverfahren zur breiten Anwendung empfohlen oder in das gesetzliche Früherkennungsprogramm aufgenommen wird, muss jedoch seine Wirksamkeit in hierfür geeigneten wissenschaftlichen Untersuchungen nachgewiesen werden. Bis jetzt gibt es bereits eine ganze Reihe epidemiologischer Studien zur Effektivität des PSA-Screenings, doch konnte ein Wirksamkeitsnachweis bisher nicht erbracht werden. Zwei große randomisierte Studien in Europa und den USA lassen für die Jahre 2005–08 erste Ergebnisse erwarten. Da epidemiologische Arbeiten belegen, dass durch PSA-Screening eine nicht unerhebliche Überdiagnostik und Übertherapie eintritt, d. h. Schaden angerichtet werden kann, ist das Ergebnis der genannten randomisierten Studien vor weitergehenden Entscheidungen unbedingt abzuwarten. Bis dahin sollte von der Anwendung des PSA-Tests zur Prostatakrebsfrüherkennung unmissverständlich abgeraten werden. Da für den Test bereits ausgiebig Werbung betrieben wurde, kommt einer gründlichen ärztlichen Aufklärung von an dem Test interessierten Personen eine Schlüsselrolle zu.     

裘法祖教授生平

Prof.Fazu Qiu,member of the Chinese Communist Party,surgery professor of Tongji Hospital,departed in Tongji Hospital,Wuhan,China,at fourteen to nine a.m,June 14,2008,after a disease.He turns 94 this year.He was the senior academician of the Academia Sinica,the illustrious medical scientist of China,and the Honorary Director of Tongji Medical College,as well as Huazhong University of Science & Technology.     

Dermatomycosis in Dogs

During the routine examination of dogs for cutaneous lesions, 205 dogs were screened for fungi other than dermatophytes. Twenty-two dogs (10.8%) revealed the presence of non-dermatophytic fungi suspicious for representing the etiologic agents of the skin lesions. The fungi isolated were Alternaria sp. (2.9%), Penicillium sp. (2.4%), Aspergillus fumigatus (2.0%), Mucor sp. (1.5%), Cladosporium sp. (1.5%) and Fusarium sp. (0.5%). No dermatophyte was isolated in association with these fungi. The incidence of these infections was found to be greater in warm and humid climate.     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.