DHPLC检测林州市高龄组和低龄组居民食管癌p53基因外显子突变谱的比较研究

目的:研究我国食管癌高发区林州市居民高龄食管癌患者与低龄食管癌患者中抑癌基因p53全部编码外显子基因突变谱的情况,比较两组患者中p53基因突变的差异。方法:留取林州市>70岁和<40岁、低年龄组食管癌患者食管癌新鲜标本51例,提取DNA,PCR扩增p53第2～11外显子。DHPLC进行突变的筛查。突变样本进行DNA纯化测序分析。结果:51例患者中,p53至少有1个外显子基因突变的36例,突变率为70.6%。高年龄组突变率为63.3%(19/30),低年龄组突变率为80.9%(17/21),两者比较无统计学意义(P>0.05)。p53有2个外显子基因突变的10例,突变率为17.6%。高年龄组突变率为26.7%(8/30),低年龄组突变率为9.5%,两者比较无统计学意义,P>0.05。结论:p53基因突变是林州市居民食管癌发生过程中的一个发生频率很高的事件。林州市居民的p53外显子突变谱中,共有15种突变类型,共计59个突变位点,其中最多的突变类型是插入碱基C。在p53基因第2～8外显子与内含子交界的非编码区有大量的基因突变。     

肺癌细胞学及血液标本表皮生长因子受体基因突变对比研究

目的:研究肺癌患者渗出液细胞学及血液标本中表皮生长因子受体(EGFR)第18、19、21外显子基因突变频率和类型以及与肿瘤组织学标本的关系。方法:收集肺癌患者渗出液细胞学标本53例及血液标本24例,提取DNA,聚合酶链反应扩增EGFR外显子18、19、21序列,用直接测序法检测基因序列,分析EGFR基因突变频率和类型以及与肿瘤组织学标本的关系。结果:53例细胞学标本检测到15例EGFR基因突变（28.3%,15/53）,18外显子突变1例,19外显子突变5例,21外显子突变9例,细胞学标本与肺腺癌组织学标本突变率（32.2%）相比,差异没有显著性（P=0.624）。24例血液标本中检测到1例突变（4.2%,1/24）,位于21外显子,血液标本与肿瘤组织学标本突变率相比,差异有显著性(P=0.006)。结论:肺癌患者渗出液细胞学标本适用于直接测序法检测EGFR突变,血液标本不适于用直接测序法检测肿瘤EGFR基因突变状态。     

DHPLC检测林州市高龄组和低龄组居民食管癌p53基因外显子突变谱的比较研究

目的：研究我国食管癌高发区林州市居民高龄食管癌患者与低龄食管癌患者中抑癌基因p53全部编码外显子基因突变谱的情况，比较两组患者中p53基因突变的差异。方法：留取林州市〉70岁和〈40岁、低年龄组食管癌患者食管癌新鲜标本51例，提取DNA，PCR扩增p53第2～11外显子。DHPLC进行突变的筛查。突变样本进行DNA纯化测序分析。结果：51例患者中，p53至少有1个外显子基因突变的36例，突变率为70．6％。高年龄组突变率为63．3％（19／30），低年龄组突变率为80．9％（17／21），两者比较无统计学意义（P〉0．05）。p53有2个外显子基因突变的10例，突变率为17．6％。高年龄组突变率为26．7％（8／30），低年龄组突变率为9．5％，两者比较无统计学意义，P〉0．05。结论：p53基因突变是林州市居民食管癌发生过程中的一个发生频率很高的事件。林州市居民的p53外显子突变谱中，共有15种突变类型，共计59个突变位点，其中最多的突变类型是插入碱基C。在p53基因第2～8外显子与内含子交界的非编码区有大量的基因突变。     

肺癌病人痰液标本p53基因突变临床流行病学分析

[目的]探讨痰液标本p53基因突变检测用于肺癌高危人群筛查和肺癌早期诊断方面的意义。[方法]应用PCR鄄SSCP对63例肺癌患者和30例肺良性疾病的肺组织和痰液细胞中p53基因5～8外显子的突变进行了检测,并采用临床流行病学的方法进行分析。[结果]肺癌病人组肺癌组织中p53基因突变率为49.2%(31/63),对照组组织中突变率为3.3%(1/30),两组差别有统计学意义(P<0.001)。肺癌组痰液标本中p53突变率为23.8%(15/63);肺良性疾病患者痰液中未发现p53基因突变。以痰液标本p53基因突变为诊断指标,诊断的敏感度为45.2%,特异度为96.8%,标化阳性预告值为93.5%,标化阴性预告值为63.9%,标化一致性为71.0%。[结论]检测痰液中p53基因突变能间接反映其在肺组织中的改变,该方法可作为肺癌高危人群筛查以及肺癌诊断的无创性手段之一。     

肺癌患者组织和痰液中p53基因、K-ras基因突变

 目的　探讨p53、K-ras基因在肺癌患者癌组织及相应痰液中改变情况及其联合检测在肺癌早期诊断中的价值。方法　对59例肺癌组织和14例肺部良性组织及相应痰液,应用PCR-SSCP-银染法检测了p53基因第5～8外显子突变情况;应用PCR-RFLP法对K-ras基因突变进行了检测。结果　p53基因在肺癌组织中突变率为37.3%,K-ras基因在肺腺癌突变率为48.0%,其它类型肺癌突变率仅为8.8%。相应痰液中两基因突变率分别为33.8%和44.0%,与组织中的突变率无明显差异,P<0.01。良性组织及相应痰液中两基因均无突变。吸烟患者的突变率(48.7%,68.5%)明显高于非吸烟患者的突变率(15.0%,11.1%),P<0.01;两基因的联合检测在肺癌的早期诊断中的价值(54.2%)明显优于单基因的检测,P<0.05。结论　痰液和组织中的基因突变率基本相似,即痰液中脱落细胞的分子遗传学改变能反映肺组织情况。因此以痰液为目标多基因的联合检测可能有助于肺癌的诊断。     

PCR-SSCP分析法检测胃癌中p27基因突变

目的　对 5例早期胃癌组织和 32例进展期胃癌及其各自的正常胃粘膜组织 ,进行p2 7抑癌基因的突变检测。方法　应用聚合酶链式反应—单链构象多态性分析 (PCR SSCP)技术进行检测。结果　在早期胃癌组织中检出突变率为 2 0 .0 %( 1/5 ) ,在进展期胃癌组织中的突变率为 2 1.9%( 7/32 )。实验结果表明 ,p2 7基因在早期胃癌与进展期胃癌中均有较高突变频率 ,两者差异无显著性 ;p2 7基因突变在胃癌中与性别、年龄以及肿瘤的位置、组织分化程度、Borrmanm分期和有无淋巴结转移无关 ;p2 7基因外显子 1是该基因突变的集中区域 ,且以第 1-90密码子区域突变率最高 ,p2 7基因外显子 2突变率最低。结论　证实了p2 7基因突变发生于早期胃癌形成阶段 ,属于胃癌发生的早期事件。     

p53基因在甲状腺癌中的突变研究

目的:为探讨p53基因突变与甲状腺癌的发生、发展及预后的关系.方法:应用PCR单链构象多态性(SSCP)分析技术,对p53基因第7,8外显子突变进行了检测和分析.结果:在37例甲状腺癌中有11例在第7.8外显子发生突变,突变率为29.9%.p53基因突变在复发的患者中显著高于未复发的患者;p53基因突变与转移、组织学类型和分化状况无显著差异.结论:p53基因的突变可能与甲状腺癌患者预后有关.     

原发性胃癌p16INK4a基因缺失和突变的研究

目的探讨p16INK4a基因缺失和突变在胃癌发病机制中所起的作用。方法采用多重PCR、PCR-SSCP和DNA测序对62例胃癌、癌旁组织及10例正常胃黏膜标本中p16INK4a基因纯合性缺失和突变进行检测。结果62例胃癌中发现p16INK4a基因第一外显子和第三外显子各有2例纯合性缺失,缺失率6.5%(4/62),PCR-SS-CP和DNA测序发现1例p16INK4a基因第一内含子区碱基插入,突变率1.6%(1/62),癌旁和正常胃黏膜均未发现缺失和突变。结论在原发性胃癌中,p16INK4a基因纯合性缺失率很低、突变罕见。     

30例配对新鲜胃癌标本中p53基因突变的研究

目的：探讨胃癌标本中p53基因外显子5～8的突变情况及其与胃癌各临床特征的关系。方法：采用银染PCR—SSCP检测30例配对新鲜胃癌手术标本中p53基因外显子5～8的突变。结果：p53基因突变检出率为46．7％（14／30），p53基因外显子5—8的突变率分别为10％、16．7％、23．3％、16．7％；p53基因突变与病人年龄、性别、原发灶部位及肿瘤分化程度之间差异没有显著性意义（P〉O．05）；但是，p53基因突变与胃癌临床分期、淋巴结转移之间差异有显著性意义（P〈O．05），进展期胃癌p53基因突变高于早期胃癌，有淋巴结转移的胃癌组织中p53基因突变高于无淋巴结转移胃癌组织。结论：p53基因突变可能参与了早期胃癌一进展期胃癌的发生发展过程，并可能是胃癌发生淋巴结转移的机制之一。     

变性高效液相色谱技术检测非小细胞肺癌患者表皮生长因子受体基因突变的研究

 目的　探讨采用变性高效液相色谱（DHPLC）技术检测表皮生长因子受体（EGFR）基因突变的优势。方法　应用DHPLC技术检测49例非小细胞肺癌（NSCLC）患者EGFR基因第19与21外显子突变情况,并应用DNA直接测序法验证DHPLC检测基因突变的准确性。结果　49例NSCLC患者中,应用DHPLC检测出13例EGFR基因突变;其中第19外显子缺失突变10例（76.92 %）;第21外显子替代突变3例（23.08 %）。DNA直接测序法突变检测结果与DHPLC一致,DHPLC检测EGFR基因突变灵敏度为100 %。结论　DHPLC技术可以快速、准确、大规模筛选EGFR基因突变。     

Oral complications of cancer and cancer therapy

Answer questions and earn CME/CNE Oral complications resulting from cancer and cancer therapies cause acute and late toxicities that may be underreported, underrecognized, and undertreated. Recent advances in cancer treatment have led to changes in the incidence, nature, and severity of oral complications. As the number of survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long‐term oral health and general well‐being. Advances in care have had an impact on previously recognized oral complications and are leading to newly recognized adverse effects. Here, the authors briefly review advances in cancer therapy, including recent advances in surgery, oral care, radiation therapy, hematopoietic cell transplantation, and medical oncology; describe how these advances affect oral health; and discuss the frequent and/or severe oral health complications associated with cancer and cancer treatment and their effect upon long‐term health. Although some of the acute oral toxicities of cancer therapies may be reduced, they remain essentially unavoidable. The significant impact of long‐term complications requires increased awareness and recognition to promote prevention and appropriate intervention. It is therefore important for the primary oncologist to be aware of these complications so that appropriate measures can be implemented in a timely manner. Prevention and management is best provided via multidisciplinary health care teams, which must be integrated and communicate effectively in order to provide the best patient care in a coordinated manner at the appropriate time. CA Cancer J Clin 2012. © 2012 American Cancer Society.     

Endocrine sequelae of cancer and cancer treatments

Introduction Exposure to cancer and its treatments, including chemotherapy and radiotherapy, may result in late adverse effects including endocrine dysfunction. Endocrine disorders are the most commonly reported long-term complications of cancer treatment, especially by adult survivors of childhood cancers. This review will explore the endocrinologic adverse effects from non-endocrine cancer therapies. Methods Searches including various Internet-based medical search engines such as PubMed, Medline Plus, and Google Scholar were conducted for published articles. Results One hundred sixty-nine journal articles met the inclusion criteria. They included case reports, systematic analyses, and cohort reports. Endocrine disorders including hypothalamus dysfunction, hypopituitarism, syndrome of inappropriate anti-diuretic hormone secretion, diabetes insipidus, growth hormone disorders, hyperprolactinemia, gonadotropin deficiency, serum thyroid hormone-binding protein abnormalities, hypothyroidism, hyperthyroidism, hypomagnesium, hypocalcemia, hyperparathyroidism, hyperparathyroidism, adrenal dysfunction, gonadal dysfunction, hypertriglyceridemia, hypercholesterolemia, diabetes mellitus, and glycosuria were identified and their association with cancer therapies were outlined. Discussion/conclusions The journal articles have highlighted the association of cancer therapies, including chemotherapy and radiotherapy, with endocrine dysfunction. Some of the dysfunctions were more often experienced than others. Especially in patients treated with radiotherapy, some endocrinologic disorders were progressive in nature. Implications for cancer survivors Recognition and awareness of endocrine sequelae of cancer treatments may permit for early detection and appropriate follow-up care for cancer survivors, thus improving their overall health and quality of life.     

Notification of cancer in breast cancer patients

The notification of the name of disease is a premise for making the system of informed consent more complete in case of cancer treatment. In Japan, however, the notification of cancer can hardly be said to have an attained social consensus. Considering that the notification can ultimately improve patients quality of life (QOL), the breast cancer group of our department informs all breast cancer patients of their diseases in principle. This paper reports and discusses the results of a survey by questionnaire on the notification of cancer in 100 patients with breast cancer. The notification of cancer was received favorably in 83% of the patients. For those who answered, the explanation on the notification was convincing and it accounted for 81%. An examination of background factors of patients who had not been convinced revealed that many of them were suffered from advanced cancer. After the notification, a human relationship with the family and friends aggravated few of them and improved in 30% (family) and 18% (friends), respectively. The notification of cancer was thus suggested to contribute to the improvement of QOL. Although 83% well received the notification of their own diseases, only 21% were affirmative for the notification of cancer in case of a member of the family. We medical professionals should make a further effort not to make the notification of cancer the pronouncement death but to make it an aid for patients to live better.     

前列腺癌和乳腺癌的对比性研究

人体一些肿瘤的生长对某些激素有一定的依赖关系,激素阻断可抑制其生长,被称为激素相关性肿瘤,如甲状腺癌、乳腺癌、子宫内膜癌及前列腺癌等.其中前列腺癌和乳腺癌为人群中发病率较高的两种恶性肿瘤,在很多方面均具有类似的特点.将二者在各方面进行对比性研究,有利于总结前列腺癌治疗方案,提高治疗效果.     

Family history of cancer among cancer patients

Family history of cancer was examined for 9,131 cancer patients who were reported to the Aichi Cancer Registry in 1979-1981, and were over 20 years old at diagnosis. The rate of patients whose parents and/or siblings had cancer of any site was 24.5%. The rate was 9.2% for father, 8.4% for mother, 6.0% for brother(s), and 5.2% for sister(s). A significant site concordance between study patient and family member with cancer was observed for cancer of the breast, colon and rectum, and stomach. The rate of family history of breast cancer patients was 3.3 times higher than the corresponding rate for other cancer patients (3.1% vs 0.9%). Similarly, the ratio was 2.2 in colon and rectum cancer (4.2% vs 1.9%), and 1.6 in stomach cancer (16.5% vs 10.1%). An increased risk of cancer was observed when both brother and sister had cancer. This may suggest an important role of environmental exposure at an early age, as well as genetic factors, in the development of cancer. The age distribution curve of the colon and rectum cancer patients who had a family history of the same cancer was found to be bimodal with the larger peak in the 40s and the smaller peak in the 70s. This may suggest a differential contribution of genetic and environmental factors to the development of colon and rectum cancer.     

Skeletal sequelae of cancer and cancer treatment

Introduction  Survivors of cancer may experience lingering adverse skeletal effects such as osteoporosis and osteomalacia. Skeletal disorders are often associated with advancing age, but these effects can be exacerbated by exposure to cancer and its treatment. This review will explore the cancer and cancer treatment-related causes of skeletal disorders. Methods  We performed a comprehensive search, using various Internet-based medical search engines such as PubMed, Medline Plus, Scopus, and Google Scholar, for published articles on the skeletal effects of cancer and cancer therapies. Results  One-hundred-forty-two publications, including journal articles, books, and book chapters, met the inclusion criteria. They included case reports, literature reviews, systematic analyses, and cohort reports. Skeletal effects resulting from cancer and cancer therapies, including hypogonadism, androgen deprivation therapy, estrogen suppression, glucocorticoids/corticosteroids, methotrexate, megestrol acetate, platinum compounds, cyclophosphamide, doxorubicin, interferon-alpha, valproic acid, cyclosporine, vitamin A, NSAIDS, estramustine, ifosfamide, radiotherapy, and combined chemotherapeutic regimens, were identified and described. Skeletal effects of hyperparathyroidism, vitamin D deficiency, gastrectomy, hypophosphatemia, and hyperprolactinemia resulting from cancer therapies were also described. Discussion/Conclusions  The publications researched during this review both highlight and emphasize the association between cancer therapies, including chemotherapy and radiotherapy, and skeletal dysfunction. Implications for cancer survivors  These studies confirm that cancer survivors experience a more rapid acceleration of bone loss than their age-matched peers who were never diagnosed with cancer. Further studies are needed to better address the skeletal needs of cancer survivors.     

Malignant transformation of thyroid cancer; poorly differentiated cancer and anaplastic cancer transformation

The prognosis of thyroid cancer depends largely on histological differentiation and clinical stage. The prognosis in anaplastic cancer is worst, in well differentiated cancer it is best; poorly differentiated cancer takes a middle position. The prognosis of patients with differentiated cancer is generally good, however, there are cases with malignant transformation such as poorly differentiated, anaplastic and squamous-cell cancer transformation. We studied the frequency and the inducement factors of malignant transformation in patients with thyroid cancer. The frequency of poorly differentiated, anaplastic and squamous-cell cancer transformation was 13.6%, 6.4% and 0.7%, respectively. In anaplastic cancer transformation, irradiation is an important factor.