复方苦参注射液在晚期恶性肿瘤患者姑息治疗中的作用

目的:探讨复方苦参注射液对晚期恶性肿瘤患者姑息治疗的近期疗效和毒副作用。方法:对45例晚期恶性肿瘤患者,采用复方苦参注射液20ml 0.9%N.S.或5%G.S.250ml静脉滴注,每日1次,3周为一疗程,连用2疗程～3疗程。结果:近期疗效:有效率4.4%,稳定率68.9%,临床受益率73.3%。止痛疗效:CR18.0%、PR23.1%、MR28.2%、NR30.8%。KPS评分:77.8%的患者有提高,提高10分者22.2%、提高20分及以上者55.6%,提高30分及以上者11.1%。除2例在输液时血管有刺激性不适外,几乎无毒副反应。结论:复方苦参注射液有一定的抗癌止痛作用,能提高患者生活质量,而又无明显毒副作用,在晚期乃至终末期恶性肿瘤患者姑息治疗中有独特治疗作用。     

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Background

Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.

Methods

P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.

Results

The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.

Conclusions

Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth.     

Malignant melanoma in Europe: changes in mortality rates (1970-90) in European Community countries

Reducing mortality, especially premature death, is a major goal of the fight against cancer. In this study, we have analyzed trends in malignant melanoma (MM) mortality in the European Community (EC) as a whole and for each country. The data (obtained from the World Health Organization data bank) have been analyzed for the period 1970-90, by age groups (20-44, 45-64, 65-74, 75+ years). Trends are presented as percentage change of mortality rate for each three-year period in comparison with the rate in the first one (1970-72). The mortality from MM in the EC as a whole increased for both genders (men, +89.2 percent; women, +72.6 percent), with statistically significant trends in all age classes. Northern countries experienced mortality changes about 30 to 50 percent less than the EC average increase. Greater changes were seen in southern European countries, in which recent standardized rates are near to those observed in northern European populations. Among Mediterranean people, the highest increase (more than fourfold) was observed in Spain. The significant increase found for the younger age class makes unlikely the risk of misclassification with other skin cancers. No future decrease in MM mortality in the EC is indicated from these data.     

Overview: Cellular plasticity,cancer stem cells and metastasis

Recently, a number of hypotheses have converged into a unified theoretical framework which addresses the most vexing aspects of cancer: metastasis, relapse and therapeutic resistance. The central component of this framework is the new paradigm of cellular differentiation, once viewed as a unidirectional process, but now recognized as a plastic process in which cancer cells can dedifferentiate into more primitive, stem-like phenotypes. This plasticity is controlled by both intrinsic biochemical processes and bi-directional environmental cues involving cancer-associated non-cancerous cells. Such plastic phenotypic shifts may influence the discontinuous behavior of cancers, in which some cancers remain dormant for months or years after therapy, only to relapse and wreak havoc. This Special Issue of Cancer Letters assembles a collection of mini-reviews describing the current knowledge of cellular plasticity and its relationship to cancer “stemness” and progression, illuminating how progress in this field may yield major benefits in overcoming resistance and thwarting metastasis.     

Biomaterial-based platforms for cancer stem cell enrichment and study

Cancer stem cells (CSCs) are a relatively rare subpopulation of tumor cell with self-renewal and tumorigenesis capabilities. CSCs are associated with cancer recurrence, progression, and chemoradiotherapy resistance. Establishing a reliable platform for CSC enrichment and study is a prerequisite for understanding the characteristics of CSCs and discovering CSC-related therapeutic strategies. Certain strategies for CSC enrichment have been used in laboratory, particularly fluorescence-activated cell sorting (FACS) and mammosphere culture. However, these methods fail to recapitulate the in vivo chemical and physical conditions in tumors, thus potentially decreasing the malignancy of CSCs in culture and yielding unreliable research results. Accumulating research suggests the promise of a biomaterial-based three-dimensional (3D) strategy for CSC enrichment and study. This strategy has an advantage over conventional methods in simulating the tumor microenvironment, thus providing a more effective and predictive model for CSC laboratory research. In this review, we first briefly discuss the conventional methods for CSC enrichment and study. We then summarize the latest advances and challenges in biomaterial-based 3D CSC platforms. Design strategies for materials, morphology, and chemical and physical cues are highlighted to provide direction for the future construction of platforms for CSC enrichment and study.     

Pregnancy and lung cancer: a case report and review of the literature

Lung cancer is a frequent pathology among women, as a result of tobacco increase. Lung cancer among pregnant women is especially rare when revealed by Pancoast-Tobias syndrome. Foetal injury is possible. The approach is multidisciplinary. Prognosis is bad.     

Breast cancer,ovarian gonadoblastoma and cervical cancer in a patient with Peutz-Jeghers Syndrome

BACKGROUND: Peutz-Jeghers Syndrome (PJS) is a rare autosomal dominant disorder characterized by gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. Patients with PJS have increased risk for gastrointestinal, breast, and female genital tract cancers. CASE: Multiple genital tract cancers in a 34-year-old woman with PJS are described. The patient, who was admitted to our department with severe vaginal bleeding, was performed right salpingo-oophorectomy because of pure gonadoblastoma in 1996. In 2003, concomitant to cervical carcinoma, breast cancer was diagnosed. Patient underwent left modified radical mastectomy due to the invasive papillary carcinoma. The patient received six cycles combination chemotherapy and radiation therapy because of stage IIIB cervical cancer. CONCLUSION(S): This is the first case report presenting PJS associated with multiple genital tract tumors including ovarian gonadoblastoma in literature. The clinical significance of these tumors in PJS patients has been reviewed.     

Polycystic ovary syndrome (PCOS)

Polycystic ovaries syndrome (PCOS) is one of the most common female hormonal disorders. Its multiple components--reproductive, metabolic, neoplasic and cardiovascular--have a major impact on the public health. Androgen excess and resistance to insulin, probably from genetic origin, are responsible for most of the clinical symptomatology. Resistance to insulin seems to be accompanied by a greater risk of glucose intolerance, type 2 diabetes, lipidic anomalies and can involve the development of cardiovascular diseases. In addition, sleep apnea syndrome is more progressively described in PCOS. Infertility, menses disorders and hirsutism often push these patients to consult their physician. A better understanding of the physiopathological mechanisms led to the emergence of new therapeutic options increasing the sensitivity to insulin. Besides the pregnancy wishes, cares aim to attenuate the marks of the hyper-androgenism (hormonal treatment and cosmetic) and to correct cardiovascular, respiratory and gynaecological risk factors. In case of infertility by anovulation, cares must be performed by trained experts to minimize the risk of ovarian hyper-stimulation syndrome and multiple pregnancies. A gradation from loose weight to clomiphene citrate ovulation induction, ovarian drilling, low dose gonadotropin, in vitro fertilisation, or in vitro maturation of oocytes should bring back good reproduction potential.     

Lynch syndrome and gynaecologic's cancer: follow-up recommendations

The Lynch syndrome or HNPCC, is due to a mutation of the genes pertaining to the system MMR. This frequency varies from 1/1000 to 1/400. It's responsible for 6% of endométrial cancers, 2% of ovarian cancers and 1 to 3% of colorectal cancers. A good knowledge of this syndrome is necessary for doing the diagnosis and adjustment of gynaecological and colorectal follow-up. The authors report four cases in Lynch syndrome family.     

Intraperitoneal chemotherapy for patients with advanced ovarian cancer: a review of the evidence and standards for the delivery of care

OBJECTIVES: To evaluate the role of intraperitoneal (IP) chemotherapy as part of primary treatment in patients with advanced ovarian cancer and to develop standards of care within the context of current clinical practice. METHODS: A multidisciplinary expert panel, convened to develop standards on the use of IP chemotherapy, searched the MEDLINE, EMBASE, and Cochrane Library databases up to December 2006 for randomized trials or published standards on the efficacy and/or delivery of IP chemotherapy. RESULTS: Eight randomized trials comparing IP chemotherapy versus intravenous (IV) chemotherapy were identified. Three trials reported statistically significant improvements in median survival of 8.0, 11.0, and 15.9 months with cisplatin-based IP chemotherapy. In one trial, the 15.9-month improvement in median overall survival (RR=0.75, 95% CI=0.58-0.97) represented a 25% reduction in the risk of death with IP chemotherapy. Severe adverse events and catheter-related complications were often dose limiting with IP chemotherapy. Using a consensus-based approach with a nationally representative panel, multidisciplinary care standards were developed to review medical and surgical criteria, the practice setting, volume requirements, and the institutional criteria required to safely deliver IP chemotherapy. CONCLUSION: The survival benefits with cisplatin-based IP chemotherapy may represent a significant improvement in the outlook for select patients with advanced ovarian cancer. The delivery of IP chemotherapy is more challenging than the IV route; however, severe adverse events and catheter-related complications may be offset through research defining the optimum treatment regimen, and the standardization of care. System-wide standards for the delivery of IP chemotherapy in Canada for patients with optimally debulked stage III ovarian cancer are offered.