Pre-Treatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma

The levels of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) can be used to predict tumor invasion, lymph node metastasis, staging and survival in patients with oral cavity cancer. The present study analyzed the relationship between pre-treatment levels of SCC-Ag and CRP in relation to clinicopathological factors in patients with pharyngolaryngeal cancer (PLC) and determined whether elevated levels of CRP and SCC-Ag were associated with tumor metabolic activity via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively recruited one hundred and six PLC patients between June 2008 and December 2011. All patients received computed tomography (CT)/magnetic resonance imaging (MRI) and FDG-PET staging analyses, and the serum levels of SCC-Ag and CRP in these patients were measured prior to treatment. A SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L were significantly associated with clinical stage (P<0.001), clinical tumor status (P<0.001), and clinical nodal status (P<0.001). The elevation of both SCC-Ag and CRP levels was correlated with the standardized uptake value (SUV) max of the tumor (≥8.6 mg/L) and lymph nodes (≥5.7 ng/ml) (P = 0.019). The present study demonstrated that the presence of high levels of both pre-treatment SCC-Ag and CRP acts as a predictor of clinical stage, clinical tumor status, and clinical nodal status in patients with PLC. Moreover, elevated levels of SCC-Ag and CRP were associated with a high metabolic rate as well as the proliferative activity measured according to the SUVmax of the tumor and lymph nodes. Therefore, elevated levels of these two factors have the potential to serve as biomarkers for the prediction of tumor aggressiveness in cases of PLC.     

Breast Cancer DNA Methylation Profiles Are Associated with Tumor Size and Alcohol and Folate Intake

Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics. Using primary breast tumors from 162 (AJCC stage I–IV) women from the Kaiser Division of Research Pathways Study and the Illumina GoldenGate methylation bead-array platform, we measured 1,413 autosomal CpG loci associated with 773 cancer-related genes and validated select CpG loci with Sequenom EpiTYPER. Tumor grade, size, estrogen and progesterone receptor status, and triple negative status were significantly (Q-values <0.05) associated with altered methylation of 209, 74, 183, 69, and 130 loci, respectively. Unsupervised clustering, using a recursively partitioned mixture model (RPMM), of all autosomal CpG loci revealed eight distinct methylation classes. Methylation class membership was significantly associated with patient race (P<0.02) and tumor size (P<0.001) in univariate tests. Using multinomial logistic regression to adjust for potential confounders, patient age and tumor size, as well as known disease risk factors of alcohol intake and total dietary folate, were all significantly (P<0.0001) associated with methylation class membership. Breast cancer prognostic characteristics and risk-related exposures appear to be associated with gene-specific tumor methylation, as well as overall methylation patterns.     

Multi-biomarker pattern for tumor identification and prognosis

In last decades, the basic, clinical, and translational research efforts have been directed to the identification of standard biomarkers associated with the degree of malignancy. There is an increasingly public health concern for earlier detection of cancer development at stages in which successful treatments can be achieved. To meet this urgent clinical demand, early stage cancer biomarkers supported by reliable and robust experimental data that can be readily applicable in the clinical practice, are required. In the current standard protocols, when one or two of the canonical proliferating index biomarkers are analyzed, contradictory results are frequently reached leading to incorrect cancer diagnostic and unsuccessful therapies. Therefore, the identification of other cellular characteristics or signatures present in the tumor cells either alone or in combination with the well-established proliferation markers emerge as an alternative strategy in the improvement of cancer diagnosis and treatment. Because it is well known that several pathways and processes are altered in tumor cells, the concept of "single marker" in cancer results incorrect. Therefore, this review aims to analyze and discuss the proposal that the molecular profile of different genes or proteins in different altered tumor pathways must be established to provide a better global clinical pattern for cancer detection and prognosis.     

Prognostic significance of nuclear morphometry in superficial bladder cancer

OBJECTIVE: To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer. STUDY DESIGN: The study included 73 patients with superficial transitional cell carcinoma of the bladder who were followed for a median of 21 months (range, 1-90). Nuclear morphometry was performed by a computer-assisted image analyzer system on hematoxylineosin-stained histologic sections and characterized by five nuclear variables: area, perimeter, major and minor diameter, and form factor. Patient charts and microscopic slides were reviewed to record tumor stage, grade and size. Tumor proliferative activity was assessed by immunohistochemical staining with Ki-67 antibody. RESULTS: None of the morphometric variables showed a significant relation to tumor progression and recurrence. Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher grade and proliferative activity. Mean nuclear area and minor diameter were associated with advanced stage. Of established prognostic factors, only histologic grade was significant in predicting progression. CONCLUSION: The results suggest that nuclear morphometry may be valuable in determining proliferative activity and may be well correlated with histologic grade in superficial bladder cancer. However, like many other potential prognostic factors, it seems to be unreliable in predicting clinical behavior.     

Estrogen receptor concentration and social factors as predictors of natural killer cell activity in early-stage breast cancer patients. Confirmation of a model

Previous work of ours has demonstrated that a significant amount of natural killer (NK) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the estrogen receptor (ER) status of the tumor and by social factors, namely, perceived social support and seeking social support as a general coping strategy. As considerable evidence has accumulated that social support in both animal and human populations may have survival value, we sought to test the reliability of this regression model, using coping and perceived support factor values obtained at 3 months after surgery to account for concurrent follow-up NK activity in this serially assessed group of patients. It was found that the most significant variable predicting NK activity at follow-up was tumor ER concentration, with higher NK activity associated with ER- status. In addition, seeking social support as a coping strategy, as well as the perceived quality of support, also entered the model to account for a significant amount of NK activity variance (multivariate F = 5.25, p less than 0.001). If, as the literature suggests, NK activity is relevant to breast cancer control, and since ER- tumors have a worse prognosis, we suggest here that perhaps such tumors are resistant to control by NK cells because they lack the ability to attract an accumulation of effector cells to the tumor site, or because blocking factors at the site of the tumor prevent local tumor control at the site of action. The finding related to social support also replicates results from an independent sample of breast cancer patients. This finding, taken together with other evidence that this social variable is associated with longer survival in breast cancer populations, underscores the potential importance of this social support variable. Our findings also suggest one possible immunological variable involved, with potential clinical significance, for this patient population.     

Fas 相关死亡结构域蛋白在乳腺癌中表达的临床病理研究

目的:探讨Fas相关死亡结构域蛋白(Fas-associated death domain protein,FADD)在乳腺癌中表达的临床病理学意义。方法:收集乳腺癌病例及相应的临床资料包括随访资料,应用免疫组织化学技术检测乳腺良性病变,有/无淋巴结转移的乳腺癌及配对淋巴结转移灶中FADD的表达,观察分析FADD表达与乳腺癌患者年龄、肿块大小、临床分期、组织学类型和分级、雌孕激素受体水平等临床病理指标间的关系。结果:免疫组化检测结果显示良性乳腺病变组中FADD的阳性表达率(85.1%,40/47)与无淋巴结转移的乳腺癌组(45.8%,38/83),伴有淋巴结转移的乳腺癌组(67.3%72/107)和淋巴结转移灶(45.8%,49/107)组织中FADD阳性表率均有显著性差异(P值分别0.001,=0.022和0.001);此外,伴有淋巴结转移的乳腺癌组中FADD阳性表达率也均与其它三组中FADD阳性表达率之间具有显著性差异(P值分别为0.003,0.001和0.022)。FADD与患者的确诊年龄(P=0.049)和淋巴结转移有显著性相关(P=0.003),与肿瘤大小、临床分期、组织学类型、组织学分级、雌孕激素受体及cerb B-2的表达情况和月经史无明显相关性(P0.05)。生存分析显示FADD阳性表达的患者较FADD阴性患者的生存期更短。结论:FADD与乳腺癌淋巴结转移和预后有关。     

初诊腋窝淋巴结阳性乳腺癌新辅助化疗后对腋窝淋巴结转阴性前哨活检的影响分析

摘要 目的：探究对初诊腋窝淋巴结阳性乳腺癌行新辅助化疗患者开展腋窝前哨淋巴结活检的临床意义。方法：选择2017年1月至2020年10月于我院接受改良根治术或保乳术治疗的100例初诊腋窝淋巴结阳性乳腺癌患者,将其中50例病理检测II B、III期行4~8个疗程新辅助化疗后实施前哨淋巴结活检患者设为研究组,将50例I、II A期直接行前哨淋巴结活检患者设为对照组,对比两组患者前哨淋巴结检出率、准确率、假阴性率和灵敏度,同时就患者病理特征与前哨淋巴结检出率的相关性开展分析。结果：（1）比较显示研究组患者与对照组患者在前哨淋巴结检出数、前哨淋巴结检出率以及前哨淋巴结假阴性率方面组间差异不大（P>0.05）;（2）病理学特征分析显示肿瘤直径以及临床N分期同新辅助化疗后患者前哨淋巴结检出阳性率密切相关（P<0.05）。结论：对初诊腋窝淋巴结阳性行新辅助化疗乳腺癌患者实施前哨淋巴结活检具有较显示的临床意义,能够较好的预测患者腋窝淋巴结状况,同时化疗前肿瘤直径、临床N分期是影响前哨淋巴结检出率的重要影响因素。     

Molecular mechanisms of perineural invasion,a forgotten pathway of dissemination and metastasis

Invasion and metastasis are key components of cancer progression. Inflammatory mediators, including cytokines and chemokines, can facilitate tumor dissemination. A distinct and largely forgotten path is perineural invasion (PNI), defined as the presence of cancer cells in the perinerium space. PNI is frequently used by many human carcinomas, in particular by pancreas and prostate cancer, and is associated with tumor recurrence and pain in advanced patients. Neurotrophic factors have been identified as molecular determinants of PNI. A role for chemokines in this process has been proposed; the chemokine CX3CL1/Fractalkine attracts receptor positive pancreatic tumor cells to disseminate along peripheral nerves. Better understanding of the neurotropism of malignant cells and of the clinical significance of PNI would help the design of innovative strategies for the control of tumor dissemination and pain in cancer patients.     

胃癌肝转移术中射频消融治疗的临床意义

目的：评估胃癌根治术同时性射频消融治疗在治疗胃癌肝转移的临床意义。方法：收集2008年1月至2010年12月19例胃癌肝转移患者,合计转移灶33个,转移灶小于4厘米,且合计不超过4个转移灶。射频消融治疗在术中超声引导下完成。Kap-lan—Meier法分析无病生存期,无肝转移生存期及总生存期。对临床病理学因子及肝转移相关因子采用Log-rank法Cox风险比例模型解析。结果：中位无病生存、无肝转移生存及总生存期为355,394及488天。有3例患者获得长期的无复发生存。单因素分析显示,较早的T分期、N分期,较少的转移灶数量,较小的转移灶直径与良好的预后相关。多因素分析提示,病灶数量与病灶直径为独立预后因子。结论：肝转移射频消融治疗安全性好,对单发的小于4cm转移灶,以及多发病灶合计直径小于4cm者射频消融治疗较为适用,可有显著生存获益。部分患者可迭临床治愈。对于胃癌肝转移的合适病例,射频消融治疗值得推广。     

Epigenetic regulation of glycosylation and the impact on chemo-resistance in breast and ovarian cancer

Glycosylation is one of the most fundamental posttranslational modifications in cellular biology and has been shown to be epigenetically regulated. Understanding this process is important as epigenetic therapies such as those using DNA methyltransferase inhibitors are undergoing clinical trials for the treatment of ovarian and breast cancer. Previous work has demonstrated that altered glycosylation patterns are associated with aggressive disease in women presenting with breast and ovarian cancer. Moreover, the tumor microenvironment of hypoxia results in globally altered DNA methylation and is associated with aggressive cancer phenotypes and chemo-resistance, a feature integral to many cancers. There is sparse knowledge on the impact of these therapies on glycosylation. Moreover, little is known about the efficacy of DNA methyltransferase inhibitors in hypoxic tumors. In this review, we interrogate the impact that hypoxia and epigenetic regulation has on cancer cell glycosylation in relation to resultant tumor cell aggressiveness and chemo-resistance.     

宫颈癌放疗患者生活质量的影响因素及与应对方式的关系研究

目的:探讨宫颈癌放疗患者生活质量的影响因素及与应对方式的关系。方法:选取2018年7月2019年11月期间我院收治的宫颈癌放疗患者139例,收集患者临床资料,采用癌症治疗功能评价系统中的宫颈癌量表(FACT-Cx)对宫颈癌患者的生活质量进行评分,采用Jalowiec的应对量表(JCS)记录并评估所有患者的应对方式,并采用Pearson相关性分析生活质量与应对方式的关系。采用单因素及多因素Logistic回归分析宫颈癌放疗患者生活质量的影响因素。结果:宫颈癌放疗患者的FACT-Cx总分与面对、乐观、姑息、依靠自我应对方式评分呈正相关(P<0.05),与情感宣泄、宿命应对方式评分呈负相关(P<0.05),与逃避、支持应对方式评分无相关性(P>0.05)。不同文化程度、年龄、化疗、肿瘤病理类型情况患者之间FACT-Cx总分比较无统计学差异(P>0.05);不同家庭月收入、肿瘤分期、下肢水肿情况、婚姻状况患者之间FACT-Cx总分比较差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,家庭月收入、肿瘤分期、下肢水肿情况、婚姻状况均是宫颈癌放疗患者生活质量的影响因素(P<0.05)。结论:宫颈癌放疗患者生活质量与应对方式存在密切联系,且家庭月收入、肿瘤分期、下肢水肿情况、婚姻状况均是其生活质量的影响因素,临床工作者应结合以上因素对患者放疗方案给予针对性调整。     

G3BP 在结肠癌中表达的临床病理学研究

目的:探讨G3BP(Ras-GTPase-activiting protein SH3 domain binding protein)在结肠癌组织中的表达及其临床病理意义.方法:用免疫组织化学技术检测50例结肠癌组织中G3BP的表达,并分析其与患者临床病理指标的关系及其对预后的影响.结果:G3BP在结肠癌中阳性表达率为72％(36/50),G3BP的阳性表达率与肿瘤分化程度、淋巴结转移、病变浸润层次及TNM分期有关.而与年龄、性别、肿瘤大小无关(P＞0.05).G3BP高表达组患者的生存时间明显短于低表达组.结论:G3BP表达与结肠癌的侵袭和转移相关,可能是结肠癌的预后差的指标.     

Overall survival in advanced breast cancer: relevance of progesterone receptor expression and DNA ploidy in fine-needle aspirates of 392 patients

Fine-needle aspiration cytology (FNAC) is essential for making a diagnosis in advanced breast cancer. The determination of hormone receptors in the material obtained is useful for predicting patient response to endocrine therapy, but the prognostic value of hormone receptor expression as well as the clinical utility of DNA flow cytometry are controversial. The aim of this prospective study with long-term follow-up (median: 81 months) was to evaluate these biomarkers in relation to overall survival in a series of 392 patients with advanced breast cancer (stage IIB, n=106; IIIA, n=66; IIIB, n=174; and IV, n=46) using FNAC. Estrogen and progesterone receptor expression was found in 65.1% and 46.1% of the tumors, respectively. Hormone receptors were not found to be associated with clinical staging. DNA aneuploidy was present in 70.9% of the cases and the median S-phase fraction (SPF) was 9.4%. There was a significant correlation of aneuploidy and high SPF with lack of hormone receptors. In univariate analysis, advanced disease stage, absence of hormone receptors, DNA aneuploidy and high SPF showed a statistically significant correlation with poor clinical outcome. In multivariate analysis, disease stage, progesterone receptors and DNA ploidy retained independent prognostic significance in relation to overall survival. These data indicate that progesterone receptor expression and DNA ploidy are independent prognostic factors in advanced breast cancer.     

DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study

Accumulating evidence has suggested the requirement for further stratification of patients in the same tumor stage according to molecular factors. We evaluate the combination of cancer stage and DNA methylation status as an indicator of the risk of recurrence and mortality among patients with colorectal cancer (CRC). A cohort study of 215 patients with CRC (mean age 64.32 years; 50.5% of men) from Tri-Service General Hospital in Taiwan examined the association between cancer stage and risk of CRC recurrence and mortality. A Cox proportional hazard model was used to analyze patient methylation status and clinical information at study entry, and their associations with CRC recurrence and mortality during follow-up. The advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status in tumor tissues, with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 9.64 (2.92–31.81), 8.29 (3.40–20.22), and 11.83 (3.49–40.12), respectively. When analyzing normal tissues, we observed similar risk of CRC recurrence with adjusted HRs (95% CI) of 10.85 (4.06–28.96), 9.04 (3.79–21.54), and 12.61 (4.90–32.44), respectively. For combined analyses, the risk of recurrence in the patients in advanced stage with DNA methylation in both normal and tumor tissues, compared with local stage with unmethylation, was increased with adjusted HR (95% CI) of 9.37 (3.36–26.09). In the advanced stage patients, methylation status and tissue subtype were associated with increased risk of 5-year cumulative CRC recurrence (p < 0.001). This study demonstrates that clustering DNA methylation status according to cancer stage and tissue subtype is critical for the assessment of risk of recurrence in CRC patients and also indicated an underlying mechanism.     

Breast-conserving therapy versus modified radical mastectomy: socioeconomic status determines who receives what--results from case-control study in Tianjin, China

Background: Despite anecdotal evidence linking socioeconomic status and choices on surgical management in breast cancer patients in China, no scientific evaluations have ever been conducted. The objective of this study was to evaluate patient factors that influence patients’ treatment options between breast cancer patients receiving breast-conserving therapy (BCT) and modified radical mastectomy (MRM). Methods: A total of 268 stage I–II breast cancer patients treated with BCT in Tianjin Cancer Hospital, from January 2005 to January 2007, were compared with 200 randomly selected breast cancer patients (controls) treated with MRM. A personal health questionnaire (PHQ) was used to assess the factors that may affect the surgical decision making. Chi-squared test and multiple logistic regressions were used to examine factors associated with BCT. Results: BCT patients who were younger and were more likely to live in urban areas had medical insurance, higher levels of education and family income. Patients with medical insurance coverage were approximately six times more likely to receive BCT than patients without medical insurance after controlling for other potentially confounding factors. Similar results were also observed for family income. The observed differences cannot be explained by clinical aspects of their disease, such as tumor stage, estrogen receptor, and lymph node involvement. Conclusion: Breast cancer patients’ socioeconomic status, rather than their clinical condition, is the predominant factor in determining whether a breast cancer patient receives BCT or not. These results provide a snapshot on how socioeconomic status influences cancer care provision in China. Future efforts should be made towards reducing discrepancies in treatment options for cancer patients caused by social class and socioeconomic status.     

PRL-3 和VEGF 在结肠癌中表达的临床病理研究

目的:探讨PRL-3和VEGF在结肠癌组织中的表达及其临床意义。方法:用免疫组织化学技术检测50例结肠癌组织及相应癌旁组织中PRL-3和VEGF的表达,并分析其与患者临床病理变量的关系及其对预后的影响。结果:PRL-3和VEGF在结肠癌组织表达上调明显高于癌旁组织,有统计学意义。PRL-3和VEGF的阳性表达率与肿瘤分化程度、淋巴结转移、及TNM分期有关。而与年龄、性别、肿瘤大小无关(P>0.05)。PRL-3和VEGF表达上调者的中位生存时间明显短于低表达者。PRL-3和VEGF表达有显著相关性。结论:PRL-3和VEGF与肿瘤分化、侵袭、转移和预后不良密切相关。     

Psychiatric morbidity and the menopause: clinical features.

A sample of 114 women from the general population aged 40-55 years were identified as possible psychiatric cases and subjected to a standardised psychiatric interview. Mean ratings for reported symptoms and observed abnormalities were assessed in relation to menopausal status. There was no evidence of any specific combination of symptoms and signs associated with the cessation of menstrual periods, though after the menopause insomnia and hypochondriacal preoccupations were more common. In comparison with matched normal controls have been previous psychiatric illness, and contact with general practitioners was more frequent. Many women developing psychiatric symptoms at the time of the menopause appear to belong to a vulnerable population who are likely to develop symptoms in relation to stress.     

Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer

Background

To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown.

Methods

This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox’s proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS).

Results

By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3'' methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis.

Conclusions

CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer.