Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

Survivin is a member of the inhibitor of apoptosis protein (IAP) family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL) recognized by CD8+ cytotoxic T lymphocytes (CTLs). We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2), general malaise (grade 1), and fever (grade 1). No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9) decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer.     

Cellular vaccine therapy for cancer

Observations that cells of the immune system are able to kill tumor cells both in vitro and in animal models have provided a compelling rationale for pursuit of a strategy whereby immune cells are administered as a therapeutic vaccine to patients with cancer. The successful outcome of this approach depends upon the ability to deliver this therapy in a manner in which a potent immune response is elicited. By harnessing the capacity of dendritic cells that are pivotal in priming the immune response and using gene therapy approaches to optimise the immune response, this may ultimately prove efficacious in the management of human cancer. Promising reports from recent clinical trials suggest that this may well be a realistic goal.     

Development of the PANVAC-VF vaccine for pancreatic cancer

PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. Vaccination is administered by subcutaneous injection followed by 4 days of local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at the vaccination site. The vaccine has been developed for patients with advanced pancreatic cancer and has now entered a randomized Phase III clinical trial. This review will describe the background of recombinant poxvirus technology for tumor vaccine development, detail the key preclinical studies supporting the regimen, review the clinical trials supporting the current Phase III study, and highlight the key challenges and future obstacles to successful implementation of PANVAC-VF for pancreatic cancer.     

Gene expression profiles associated with advanced pancreatic cancer

Few studies have addressed the expression profiles associated with progression of pancreatic cancer to advanced disease. Towards this end, we performed expression profiling of a series of normal pancreas, pancreatitis and cancer tissues representing early stage resected pancreatic cancers (stages pT2/T3), late stage unresectable cancers (stage pT4) and matched metastases to a variety of organ sites. Microarray data was analyzed using linear modeling of microarray data (LIMMA), and differentially expressed genes were subjected to Gene Set Enrichment Analysis (GSEA). While robust differences were found in primary cancers as compared to normal pancreatic tissues, no differences were found between primary cancers and metastases, whether using matched or unmatched samples. When resected pancreatic cancers were specifically compared to advanced pancreatic cancers, significant differences in gene expression were found associated with growth at the primary site. These differentially expressed genes were most prominent in gene classes that related to MAPK and Wnt pathway, metabolism, immune regulation, cell-cell and cell-matrix interactions within the infiltrating carcinoma. One candidate upregulated gene (MXI1) was validated as having increased expression in advanced stage (T4) carcinomas by real-time PCR (p<0.05) and immunolabeling (p<0.003). We conclude that in addition to the robust changes in expression that accompany pancreatic carcinogenesis additional specific changes occur in association with growth at the primary site. By contrast, metastatic spread is not accompanied by reproducible changes in gene expression. These findings add to our understanding of pancreatic cancer and offer new topics for investigation into the aggressive nature of this deadly tumor type.     

Integrative therapy for advanced pancreatic cancer using Kampo and western medicine: A case report

A 45-year-old male patient diagnosed as stage IVa pancreatic cancer received anti-cancer treatment with chemotherapy and radiotherapy. During the treatment, he complained of nausea, appetite loss, and fatigue. He received a Kampo diagnosis of qi deficiency, blood stasis, and heat with phlegm; consequently, qi supplementation, smoothing blood, and relieving fever were initiated using Juzentaihoto and Keppuchikuoto. After this treatment, the symptoms showed remarkable improvement. However, computed tomography revealed multiple lung nodules. We prescribed crude drugs with anti-cancer effects, including Scutellaria barbata and Oldenlandia diffusa. These drugs led to slowed development of lung metastases that could be surgically resected. He survived for 7 years after the advanced diagnosis without loss of quality of life. Kampo medicine may be useful for disease control and supportive care in advanced pancreatic cancer patients.     

胰腺癌分子靶向治疗的研究进展

胰腺癌是一种恶性度极高的肿瘤,85%的患者在就诊时已丧失手术机会,而常规化疗及放疗等治疗措施的疗效并不理想。随着分子生物学研究的进展,表皮生长因子受体抑制剂、血管内皮生长因子抑制剂等分子靶向药物的研究成为热点之一。本文就胰腺癌分子靶向治疗研究的进展做一简要综述。     

Preoperative chemoradiation and pancreaticoduodenectomy with portal vein resection for localized advanced pancreatic cancer

Pancreatic adenocarcinoma is a common disease that is rarely cured. Surgical resection remains the only treatment modality that has a curative potential, although the majority of patients are unsuitable for resection at the time of diagnosis. Chemoradiation therapy prior to a pancreaticoduodenectomy ensures that a patient who undergoes a complete resection multimodality therapy, avoids a resection in patients who have a rapidly progressive disease, and allows radiation therapy to be given to well oxygenated cells before, surgical devasculation. This permits the chance of resection of an unresectable pancreatic cancer by downstaging. A patient with cytologic proof of localized adenocarcinoma of the pancreatic head received an intravenously chemoradiation (Taxol, 50 mg/m2 intravenously for 3 hours week on 5 cycles, of Gemcytabine 1000 mg/m2/day intravenously for 3 days week on 2 cycles, of 4500 cGy) with the intention of proceeding to a resection operation, restaging was performed by computed tomography, magnetic resonance imaging from 5 weeks every months due to ongoing decreasing of tumor size after the chemoradiation. At laparotomy, the patient didn't have suspected metastatic disease, the tumor size was 2 X 3 cm on the pancreas head and was infiltrating into the portal vein for about 3 cm length on right side. A pancreaticoduodenectomy along with a portal vein and superior mesenteric vein resection was done and then reconstruction of a vascular anastomosis by using the right side of the internal jugular vein. Perioperative complications didn't occur. In conclusion, preoperative chemoradiation of a localized advanced pancreatic tumor has no added risk to the operative complications and the prospects for resectability are enhanced.     

Meta-analysis of FOLFIRINOX regimen as the first-line chemotherapy for locally advanced pancreatic cancer and borderline resectable pancreatic cancer

Clinical and Experimental Medicine - The study aimed to evaluate the effectiveness of the first-line chemotherapy FOLFIRINOX in treating pancreatic cancer. Pertinent studies were derived from the...     

Minimally invasive surgery for patients with advanced stage endometrial cancer

Objective: Compare the oncologic outcomes of patients with advanced stage endometrial cancer who were staged by minimally invasive surgery with the outcomes of patients who underwent open surgery.Methods: Data from 138 patients with advanced stage endometrial cancer who were treated between January 2009 and January 2019 were reviewed. The patients'' data were retrieved from five institutions. The patients were divided into two groups: those who underwent open surgery and those who underwent minimally invasive surgery. Tumor characteristics, recurrence rate, disease-free survival, and overall survival were compared according to surgical approach.Results: Among the 138 patients included in this study, 72 underwent open surgery (52.2%) and 66 underwent MIS (47.8%). In patients with advanced-stage endometrial cancer, the recurrence rate was significantly higher among those who underwent open surgery (43.1% vs. 25.8%, p = 0.033). Patients with advanced-stage endometrial cancer who underwent open surgery had a significantly lower disease-free survival (p = 0.029) than those who underwent minimally invasive surgery, however, the overall survival (p = 0.051) was similar between the two groups.Conclusion: Minimally invasive surgery showed better survival outcomes when compared to open surgery in advanced-stage EC patients irrespective of the histologic type.     

替吉奥单药对比吉西他滨单药一线治疗老年晚期胰腺癌的临床研究

目的：比较替吉奥单药与吉西他滨单药一线治疗老年人晚期胰腺癌的近期疗效、无进展生存和安全性。方法：回顾性分析我院自2009年1月-2014年8月收治的老年晚期胰腺癌患者44例,一线采用替吉奥单药或吉西他滨单药化疗。替吉奥组21例,吉西他滨组23例。每例患者至少接受化疗2个周期以上。每2个周期复查CT,根据实体瘤疗效评价标准（Response Evaluation Criteria In Solid Tu m o r s,R ECI ST）和美国国家癌症研究所化疗毒性分级标准（Nat i o n a l Ca n c e r In s t i t u te Co m m o n Te r m i n o l o g y C r i t e r i a Fo r A d v e r s e Ev e n t s,N C I-C TC A E）对两组治疗的近期疗效、无进展生存（progression-f ree sur v ival,PFS）和不良反应进行评估。结果：44例老年晚期胰腺癌患者经替吉奥或吉西他滨单药化疗,两组的有效率（objective response rate,ORR）及疾病控制率（disease control rate,D CR）相似,差异无统计学意义（P〉0.05）。替吉奥组中位PFS3.6月,吉西他滨组中位PFS4.0月,差异无统计学意义（P〉0.05）。替吉奥组的骨髓抑制情况明显低于吉西他滨组,其中中性粒细胞减少差异有统计学意义（P=0.01）。其它的药物相关不良反应主要为1-2级胃肠道反应和肝功能异常。结论：替吉奥单药对比吉西他滨单药一线治疗老年晚期胰腺癌,两组疗效相似,但替吉奥的化疗毒性反应明显较小,患者能耐受,口服给药方便,可推荐作为老年晚期胰腺癌的一线化疗方案,尤其可能适用于PS评分2分的不能耐受吉西他滨或其他联合方案的老年晚期胰腺癌患者。     

替吉奥胶囊在晚期大肠癌患者维持治疗中的临床观察

目的：观察替吉奥在晚期大肠癌(结直肠癌)患者维持治疗的疗效和不良反应。方法：38例确诊为晚期大肠癌的患者,经过氟尿嘧啶类组成的联合化疗方案化疗4~6周期,化疗后部分缓解(partial response,PR)或疾病稳定(stable disease,SD)的患者,被分为治疗组和观察组。治疗组采用替吉奥单药口服维持治疗,连用2周,停药1周,3周为一个周期。观察组不予任何治疗。每2周期后行影像学检查评价疗效、不良反应及随访情况。结果：治疗组总有效率为45.5%,临床受益率为81.8%,中位无疾病进展时间为5.7个月,中位总生存期为10.9个月;观察组总有效率为31.3%,临床受益率为68.8%,中位无疾病进展时间为3.1个月,中位总生存期为6.7个月;两组近期疗效、中位无疾病进展时间及中位生存期比较差异有统计学意义(P<0.05)。毒副反应主要为Ⅰ~Ⅲ度骨髓抑制、消化道反应、肝功能损伤及手足综合症。结论：替吉奥在晚期大肠癌患者维持治疗中效果肯定、生存质量高、毒副作用小。     

Hamming clustering techniques for the identification of prognostic indices in patients with advanced head and neck cancer treated with radiation therapy

The aim of the study is to demonstrate the usefulness of a new, non-linear classifier method, called Hamming clustering (HC), in selecting prognostic variables affecting overall survival in patients with head and neck cancer. In particular, the aim is to identify whether tumour proliferation parameters can be predictive factors of response in a set of 115 patients that receive either alternating chemo-radiotherapy or accelerated or conventional radiotherapy. HC is able to generate a set of understandable rules underlying the study objective; it can also select a subset of input variables that represent good prognostic factors. HC has been compared with other standard classifiers, providing better results in terms of classification accuracy. In particular, HC obtains the best accuracy of 74.8% (sensitivity of 51.1% and specificity of 91.2%) about survival. The rules found show that, besides the classical, well-known variables concerning the tumour dimension and the involved lymphonodes, some biological parameters, such as DNA ploidy, are also useful as predictive factors.     

胰腺癌围手术期局部化疗与疗效观察

目的 观察胰腺癌的局部化疗效果。方法 １３例胰腺癌患者在Ｂ超引导 下，经皮或／或术中穿刺胰痛肿块注药化疗共４７例次。结果 本组除２例晚期胰癌分别存活８２天和３８天后死于多器官功能衰竭（ＭＯＦ）外，均好转治愈（８９．６％）。结论 该方法不仅提高了胰腺癌的好转治愈率和生活质量， 同程度地延长了存活时间，对手术切除困难或无法根治者增加了新的治疗手段。     

晚期喉癌介入治疗的应用解剖

目的为喉部肿瘤介入治疗提供血管形态学资料.方法 解剖观察成年尸体标本16 例(32侧),分别测量了股动脉至甲状腺上、下动脉开口处的距离,甲状腺上、下动脉的开口处外径等.结果股动脉至左侧甲状腺上动脉的距离为(62.6±7.8 )cm,右侧为(61.3±7.2) cm;至左侧甲状腺下动脉为(52.5±6.9)cm,右侧为(51.1±5.8)cm.甲状腺上、下动脉的外径分别为(2.1±0.6)mm和(2.3±1.2)mm.结论喉部动脉血供主要来自甲状腺上、下动脉分别发出的喉上、下动脉支供应.本项研究为临床介入治疗喉部肿瘤提供了动脉形态学依据.     

NGS-based oncogenic mutations analysis in advanced colorectal cancer patients improves targeted therapy prediction

Background

Characterization of genetic alterations has been revealed to be important to predict the outcomes of targeted therapy in cancer. We here aimed to assess the mutation profiling of 526 colorectal cancer (CRC) patients by next-generation sequencing (NGS) to enable a more personalized anti-EGFR treatment.