肿瘤化学预防药物的临床前筛选体系

简要描述了国外在开展肿瘤化学预防药物研究时所使用的一系列临床前筛选试验方法 ,这些方法组成了一个比较系统的肿瘤化学预防药物筛选体系 ,这一体系将会在我国的癌症预防药物特别是中药癌症预防药物研究中起到借鉴作用。

Ski and SnoN, potent negative regulators of TGF-β signaling

Ski and the closely related SnoN were discovered as oncogenes by their ability to transform chicken embryo fibroblasts upon overexpression. While elevated expressions of Ski and SnoN have also been reported in many human cancer cells and tissues, consistent with their pro-oncogenic activity, emerging evidence also suggests a potential anti-oncogenic activity for both. In addition, Ski and SnoN have been implicated in regulation of cell differentiation, especially in the muscle and neuronal lineages. Multiple cellular partners of Ski and SnoN have been identifed in an effort to understand the molecular mechanisms underlying the complex roles of Ski and SnoN. In this review, we summarize recent findings on the biological functions of Ski and SnoN, their mechanisms of action and how their levels of expression are regulated.

E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome

AIM： To investigate the changes that occur in E-cadherin expression during the process of metastasis in colorectal cancer.METHODS： E-cadherin expression was detected by immunohistochemistry and two indices of expression were calculated which reflected the level of expression and the locations （membrane and cytoplasm）. Univariate and multivariate survival analyses were used to assess the value of these two E-cadherin indices as predictors of both disease-free （DFS） and disease-specific （DSS） survival. RESULTS： E-cadherin membrane index （MI）, but not cytoplasmic index （CI）, was significantly higher in primary tumors than their metastases （P = 0.0001）. Furthermore, both primary tumor MI and CI were higher among the patients who developed subsequent metastasis （P = 0.022 and P = 0.007, respectively）. Interestingly, both indices were higher in liver metastase compared to other anatomic sites （MI, P = 0.034 and CI, P = 0.022）. The CI of the primary tumors was a significant predictor of DFS （P = 0.042, univariate analysis）, with a strong inverse correlation between CI and DFS （P = 0.006, multivariate analysis）. Finally, the MI of primary tumor proved to be a significant independent predictor of DSS, with higher indices being associated with a more favorable outcome （P = 0.016）. CONCLUSION： Examination of E-cadherin expression and distribution in colorectal tumors can be extremely valuable in predicting disease recurrence. The observation that aberrant cytoplasmic expression of E-cadherin can predict disease recurrence is obviously of great importance for both patients and clinicians, and significantly affects decisions concerning the therapy and management of the patients.

Adjuvant and neoadjuvant treatment in pancreatic cancer

Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United States.Surgical resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at presentation.Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy.Currently there is no consensus around the world on what constitutes"standard"adjuvant therapy for pancreatic cancer.This controversy derives from several studies,each fraught with its own limitations.Standards of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe.Regardless of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients.In this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

Depression and anxiety levels in therapy-nave patients with inflammatory bowel disease and cancer of the colon

AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa including 20 males and 10 females, aged 39-78, underwent a structured interview, which comprised Hamilton’s Depression Rating Inventory, Hamilton’s Anxiety Rating Inventory and Paykel’s Stressful Events Rating Scale. RESULTS: Patients of the IBD group expressed both depression and anxiety. Depressive mood, sense of guilt, psychomotor retardation and somatic anxiety were also more pronounced in IBD patients. The discriminant function analysis revealed the total depressive score was of high importance for the classification of a newly diagnosed patient into one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher levels of depression and anxiety. Moreover, a psychiatrist in the treatment team is advisable from the beginning.

Metastasis-associated long noncoding RNAs in gastrointestinal cancer: Implications for novel biomarkers and therapeutic targets

Long non-coding RNAs(lnc RNAs), a newly discovered class of nc RNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lnc RNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lnc RNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lnc RNAs, and evaluate the p o t e n t i a l r o l e s o f l n c R N A s a s n o v e l d i a g n o s t i c biomarkers and therapeutic targets in gastrointestinal cancer.

Gastric carcinogenesis

Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates:at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called "intestinal metaplasia"; phenotypic antralization of fundic units, which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cellzone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research.

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

Survival rates for metastatic lung cancer, including non-small cell lung cancer （NSCLC） and small cell lung cancer （SCLC）, are poor with S-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-- with its capacity for memory, exquisite specificity and central and universal role in human biology--immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

Primary signet ring cell carcinoma of the appendix:A rare case report and our 18-year experience

Primary adenocarcinoma of the appendix is a rare malignancy that constitutes 〈 0.5% of all gastrointestinal neoplasms. Moreover, primary signet ring cell carc noma of the appendix is an exceedingly rare entity. We have encountered 15 cases of primary appendiceal cancer among 3389 patients who underwent appen- dectomy over the past 18 years. In the present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with ovarian metastases and unresectable peritoneal dissemination occurring in a 67-year-old female patient. She underwent ap- pendectomy and bilateral salpingo-oophorectomy with a laparoscopy procedure. She then received palliative systemic chemotherapy with 12 cycles of oxaliplatin, 5-flurorouracil, and leucovorin （FOIFOX-4）. The patient currently is well without progression of disease 12 mo after beginning chemotherapy.

Black phosphorous nanosheets−gold nanoparticles−cisplatin for photothermal/photodynamic treatment of oral squamous cell carcinoma

To improve five-year survival rate of oral squamous cell carcinoma(OSCC),the development of a novel composite material of black phosphorus nanosheets(BPNSs)and gold nanoparticles(AuNPs)for tumor treatment was carried out.The purpose of this study is to evaluate the cytostatic effects of BPNSs,AuNPs loaded with cisplatin(CDDP)on human tongue squamous cell carcinoma cells lines(SCC-9),and 7,12-dimethylbenz anthracene induced cheek squamous cell carcinoma was validated in golden hamsters animal models.The results showed that BPNSs could efficiently inhibit the metastasis and growth of OSCC compared with CDDP and AuNPs.And a combination composite of AuNPs−BPNSs loaded with CDDP could more effectively inhibit the metastasis and growth of OSCC,which might be due to the high drug-loading capacity,excellent photothermal properties and the combination of photodynamic and photothermal therapy of BPNSs and AuNPs,as well as the synergistic effects of AuNPs,BPNSs and CDDP.

Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2,interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.

Impact of adjuvant chemotherapy delay on survival in cancer breast patients

Objective： The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. It is usually prescribed within 2-3 months after definitive surgery. The aim of this retrospective study was to assess the impact of adjuvant chemotherapy （CT） delay beyond 3 weeks （ 21 days） in premenopausal patients with ER-absent tumors being treated for early stages breast cancer on overall survival （OS） and disease-free survival （DFS）. Methods： This retrospective study was conducted through revision of medical records of premenopausal patients diagnosed with early stage ｜-｜IIA breast cancer and ER-absent tumors who received adjuvant CT after definitive surgery at the Department of Clinical Oncology, Ain-Shams University Hospitals. Results： Between 2005 and 2008, 105 patients were retrospectively analyzed and included. Patients were divided into 2 groups： Group A including 48 patients who started adjuvant CT 〈 21 days of surgery and group B which included 57 patients who had CT delay 〉 21 days. Both groups were matched demographically. Comparisons of overall survival, and disease-free survival between group A and group B patients all favored group A. At 5-year the OS rates were 87% and 73% for groups A and B respectively （P = 0.001）, while DFS rates were 85% and 64% in groups A and B respectively （P = 0.001）. Analysis of other prognostic factors （age, T, N, grade, HER2 status, surgery type, CT type, local radiotherapy received） were analyzed. Only nodal status predicted for worse DFS （P = 0.05） and OS （P = 0.006）. Conclusion： Delay in initiating adjuvant chemotherapy for early stage breast cancer patients with ER-absent tumors was associated with a decrease in both OS and DFS rates.

Concomitant gastric adenocarcinoma and stromal tumor in a woman with polymyalgia rheumatica

Gastrointestinal stromal tumors （GISTs） are rare neoplasms （1%） of the gastrointestinal tract and to our knowledge only rare cases of synchronous presentation of gastric carcinomas and GISTs are reported in the literature. A 72-year-old female with a simultaneous presentation of gastric adenocarcinoma and GIST is presented. Moreover, due to polymyalgia rheumatica the patient received corticosteroids as treatment for the last 3 years. The concomitant occurrence of these neoplasms may involve common carcinogenic factors and there could be an association with polymyalgia rheumatica either as a paraneoplastic presentation or due to its treatment with corticosteroids.

Evolving role of adiponectin in cancer-controversies and update

Adiponectin(APN), an adipokine produced by adipocytes, has been shown to have a critical role in the pathogenesis of obesityassociated malignancies. Through its receptor interactions, APN may exert its anti-carcinogenic effects including regulating cell survival, apoptosis and metastasis via a plethora of signalling pathways. Despite the strong evidence supporting this notion, some work may indicate otherwise. Our review addresses all controversies critically. On the whole, hypoadiponectinaemia is associated with increased risk of several malignancies and poor prognosis. In addition, various genetic polymorphisms may predispose individuals to increased risk of obesity-associated malignancies. We also provide an updated summary on therapeutic interventions to increase APN levels that are of key interest in this field. To date efforts to manipulate APN levels have been promising, but much work remains to be done.

Single-cell analyses of circulating tumor cells

Circulating tumor cells(CTCs) are a population of tumor cells mediating metastasis, which results in most of the cancer related deaths. The number of CTCs in the peripheral blood of patients is rare, and many platforms have been launched for detection and enrichment of CTCs. Enumeration of CTCs has already been used as a prognosis marker predicting the survival rate of cancer patients. Yet CTCs should be more potential. Studies on CTCs at single cell level may help revealing the underlying mechanism of tumorigenesis and metastasis. Though far from developed, this area of study holds much promise in providing new clinical application and deep understanding towards metastasis and cancer development.

Prognostic value of circulating tumor cells in esophageal cancer

AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells(CTCs) can be used as a prognostic marker of esophageal cancer.METHODS Pub Med, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival(OS). The meta-analysis was performed using the random effects model, with hazard ratio(HR), risk ratio(RR) and 95% confidence intervals(95%CIs) as effect measures.RESULTS Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression(HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS(HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage(RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage(RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer.CONCLUSION Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted.

Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies

Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warhurg＇s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.

Peutz-Jeghers syndrome with small intestinal malignancy and cervical carcinoma

We report a case of 30-year-old woman with Peutz- Jeghers syndrome (PJS). Because of small intestinal obstruction, she received the small intestinal polypectomy in 2001, and the pathological diagnosis was Peutz-Jeghers polyp canceration (mucinous adenocarcinoma, infiltrating full-thickness of the intestine). The patient did not feel uncomfortable after 6 mo of chemotherapy and other management. We kept a follow-up study on her and found that she suffered from cervical cancer in 2007, with a pathological diagnosis of cervical adenosquamous carcinoma.The patient presented with typical features of PJS, but without a family history. The PJS accompanied with both small intestinal and cervical malignancies has not been reported so far in the world.

Predicting tumor response after preoperative chemoradiation using clinical parameters in rectal cancer

AIM: To evaluate the clinical parameters and identify a better method of predicting pathological complete response (pCR). METHODS: We enrolled 249 patients from a database of 544 consecutive rectal cancer patients who underwent surgical resection after preoperative chemoradiation therapy (PCRT). A retrospective review of morphological characteristics was then performed to collect data regarding rectal examination findings. A scoring model to predict pCR was then created. To validate the ability of the scoring model to predict complete regression.RESULTS: Seventy patients (12.9%) achieved a pCR. A multivariate analysis found that pre-CRT movability (P = 0.024), post-CRT size (P = 0.018), post-CRT morphology (P = 0.023), and gross change (P = 0.009) were independent predictors of pCR. The accuracy of the scoring model was 76.8% for predicting pCR with the threshold set at 4.5. In the validation set, the accuracy was 86.7%. CONCLUSION: Gross changes and morphological findings are important predictors of pathological response. Accordingly, PCRT response is best predicted by a combination of clinical, laboratory and metabolic information.

Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.