MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response

Abstract

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with an extremely low median survival rate of 12–15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to the treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain-specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and miR-338-5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased cell proliferation, increased cell cycle arrest, and apoptosis in comparison to irradiation-only cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, and ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation, and cell cycle regulation. To our knowledge, this is the first study to describe the role of miR-338-5p in GBM and its potential to improve the sensitivity of GBM to radiation.

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The interplay between autophagy and apoptosis induced by tanshinone IIA in prostate cancer cells

Abstract

Tanshinone IIA (T2A), a derivative of phenanthrenequinone and also the major active ingredient of Danshen, has been paid extensive attention as a promising cancer therapy for its potential anti-cancer activities. In this study, the apoptosis and autophagy of human prostate cancer PC-3 cells were observed after 5 μM T2A treatment, as well as their relevance. Mitochondrial-dependent apoptosis was firstly detected through morphological observation and biochemical analysis. Meanwhile, 5 μM T2A successfully triggered the autophagy of PC-3 cells, indicated by increased expression of Beclin1, and LC3 II. Validation experiments were conducted to further consolidate T2A's contribution to autophagy: Pretreatment with autophagy inhibitor 3-methyladenine (3-MA) provided protection against autophagy and enhanced T2A-induced apoptosis. Besides, the apoptosis suppressor z-VAD-fmk failed to facilitate the formation of autophagic vacuoles, which also proved the T2A-induced autophagy independent of apoptosis. Moreover, the reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) efficiently inhibited the expression of Beclin1, LC3-II, and cleaved caspase-3, which indicated apoptosis and autophagy with dependence on intracellular ROS production. Taken together, these results demonstrated that autophagy is the cytoprotective mechanism in this experimental system, and the ROS resulted from T2A treatment played a critical role in apoptosis and autophagy initiation.

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Decreased long noncoding RNA MIR31HG is correlated with poor prognosis and contributes to cell proliferation in gastric cancer

Abstract

Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in the development of several human cancers. MIR31HG, an lncRNA located in 9p21.3 and 2166 bp in length, has been found to be upregulated in breast cancer and contributes to cell proliferation and invasion. However, the expression pattern and biological function of MIR31HG in gastric cancer are still not well documented. In this study, we found that MIR31HG expression is decreased in gastric cancer tissues and associated with larger tumor size and advanced pathological stage. Patients with lower MIR31HG expression had a relatively poor prognosis. Furthermore, ectopic over-expression of MIR31HG could inhibit gastric cancer (GC) cell proliferation both in vitro and in vivo, while knockdown of MIR31HG by small interfering RNA (siRNA) promoted cell proliferation in GC cells partly via regulating E2F1 and p21 expression. Our findings present that decreased MIR31HG is involved in GC development and could be identified as a poor prognostic biomarker in GC patients.

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The impact of coexistent Hashimoto’s thyroiditis on lymph node metastasis and prognosis in papillary thyroid microcarcinoma

Abstract

The impact of coexistent Hashimoto's thyroiditis (HT) on lymph node metastasis (LNM) and prognosis in papillary thyroid microcarcinoma (PTMC) remains controversial. We evaluated the association of coexistent HT with clinicopathologic parameters, LNM, and prognosis by retrospectively reviewing a series of consecutive patients treated for PTMC at Fudan University Cancer Center from January 2005 to December 2010. Of all 1,250 patients with complete data for analysis, 364 (29.1 %) had coexistent HT (HT group) and 886 patients (70.9 %) had no evidence of HT (control group). The HT group had higher proportion of female (87.9 vs 70.1 %) patients, higher mean level of thyroid-stimulating hormone (TSH) (2.39 vs 2.00 mIU/L), and lower incidence of extrathyroidal extension (7.4 vs 11.7 %) than those in the control group. However, the incidence of LNM and recurrence was similar between the two groups, and HT was not associated with LNM and recurrence. A series of clinicopathologic factors identified for predicting LNM and recurrence in the control group did not show any prediction in the HT group. In summary, this study suggested that coexistent HT had insignificant protective effect on LNM and prognosis in PTMC, which was inconsistent with prior studies. Further studies aiming to determine novel predictors are recommended in PTMC patients with coexistent HT.

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Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner

Abstract

RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.

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The variation and clinical significance of hormone receptors and Her-2 status from primary to metastatic lesions in breast cancer patients

Abstract

The objective of this study is to investigate how the change of hormone receptor (HR) and human epidermal growth factor receptor-2 (Her-2) status is related to patients' clinical features. One hundred ninety-three cases of patients treated at general hospital of PLA from 2000 to 2015 with advanced breast cancer were included. All patients developed recurrence that were re-biopsied and had complete pathological profile both at initial diagnosis and at relapse. HR status before and after relapse were available for all patients, while only 143 cases had Her-2 status at the two stages. The changes of ER, PR, and Her-2 status and their association with clincopathological factors and DFS were analyzed. The discordant rates of ER, PR, and Her-2 status between primary breast cancer and recurrent tumor were 34.2, 38.3, and 16.8 %, respectively. At relapse, the rates of gain of ER and PR positivity were 10.9 and 13.5 %, respectively; the rates of loss of ER and PR positivity were 23.3 and 24.9 %. Loss of positivity was more frequent than gain of positivity (p _ER < 0.000, p _PR = 0.001). Among patients with Her-2 negative primary tumors, 15.4 % acquired Her-2 positivity at relapse; and among Her-2 positive patients at initial diagnosis, 1.4 % turned to Her-2 negative at relapse; gain of positivity was more frequent than loss of positivity (p < 0.000). Patients with tumor larger than 2 cm in diameter were more likely to experience change of Her-2 status (25.0 vs 5.8 %, p = 0.005). Yet, the change of ER/PR was not significantly associated with the size of primary tumor. Patients with ER positive recurrent disease and PR positive primary tumor had a DFS of more than 40 months. Compared to patients who maintained PR negative, patients who gained PR positivity at relapse had significantly longer DFS by 8.5 % (35.2 vs 26.7 months, p = 0.024). Patients losing ER positivity at relapse had shorter DFS by 7.8 months compared to those with stable ER positive tumors; patients gaining ER positivity experienced longer DFS by 8.3 months; but both differences were not statistically significant. Loss of Her-2 positivity was associated with longer DFS by 13.8 months as opposed to stable Her-2 status, without statistical significance. For patients with Her-2 negative primary tumor, the changes of Her-2 status were not associated with DFS. 34.2, 38.3, and 16.8 % of breast cancer patients had their ER, PR, and Her-2 status changed after recurrence, and these changes of receptor status were associated with DFS to some degree. Gain of PR positivity at relapse was significantly correlated with longer DFS.

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Immunomodulatory and cellular antioxidant activities of pure compounds from Teucrium ramosissimum Desf.

Abstract

Evaluation of the immunomodulatory activity of plant compounds is an interesting and growing area of research. Teucrium ramosissimum Desf. is a native and endemic medicinal plant from the South of Tunisia traditionally used for the treatment of many diseases. The anti-inflammatory activity of apigenin-7-glucoside, genkwanin, and naringenin isolated from T. ramosissimum were assayed. The phagocytic activities of macrophage and lymphocyte proliferation were investigated in the absence and presence of mitogens (lipopolysaccharide [LPS] or lectin). Depending on the concentrations, the compounds affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide (NO) release. The tested compounds enhance significantly splenocyte proliferation, either with or without mitogen stimulation. In studies to assess any potential effects of apigenin-7-glucoside, genkwanin, and naringenin on innate immunity, the results showed that these compounds significantly enhanced the killing activity of natural killer (NK) cells and cytotoxic activity of the T lymphocyte (CTL) isolated from splenocytes. These results suggest that T. ramosissimum compounds such as apigenin-7-glucoside, genkwanin, and naringenin may be potentially useful for modulating immune cell functions in physiological and pathological conditions.

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Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion

Abstract

Rab25 was reported to be associated with several human cancers and malignant biological behavior of cancer cells. The goal of the present study was to determine its expression pattern and biological function in human hepatocellular carcinoma (HCC). We examined Rab25 protein in 92 cases of HCC tissues and 3 HCC cell lines. The results showed that Rab25 was upregulated in HCC tissues and cells compared with normal liver tissues and cell line. Rab25 overexpression correlated with advanced tumor stage and nodal metastasis. Rab25 small interfering RNA (siRNA) was employed in Bel7402 and SK-Hep-1 cell lines. Cell Counting Kit-8 (CCK-8) assay and colony formation assay showed that Rab25 depletion blocked cell growth rate and inhibited colony formation ability. Transwell assay showed that Rab25 depletion negatively regulated the invading ability of HCC cells. To explore the possible mechanisms, we checked several signaling pathways and found that Rab25 depletion downregulated AKT phosphorylation. In addition, luciferase reporter assay showed that Rab25 depletion inhibited the Wnt signaling pathway and its target genes such as cyclin D1, c-myc, and MMP7. In conclusion, Rab25 is overexpressed in human HCC and contributes to cancer cell proliferation and invasion possibly through regulation of the Wnt signaling pathway.

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Monitoring bone and soft-tissue tumors after carbon-ion radiotherapy using 18 F-FDG positron emission tomography: a retrospective cohort study

Abstract

Background

The results of treatment for malignant bone and soft-tissue tumors arising from the deep trunk and pelvis are still not acceptable due to the relatively high recurrence and low overall survival rates. Recently, carbon ion radiotherapy (CIRT) was applied for several malignancies, including bone and soft-tissue sarcomas, and provided favorable results. However, it has been unclear what modalities should be used for evaluating the response and for the follow-up of these patients. Here, we analyzed the methods used to predict local recurrence and to find local failures or metastases.

Methods

We analyzed 37 patients with bone and soft-tissue tumors who received CIRT at our institute. The patients were examined with FDG positron emission tomography (PET) and enhanced MRI before and three months after CIRT. The pre-treatment maximum standardized uptake value (SUVmax), and that three months after treatment, the difference between the pre- and post-CIRT SUVmax, the ratio of the post- to pre-SUVmax in FDG-PET and the size of the tumors were evaluated as predictors for local recurrence. FDG-PET and enhanced MRI were used to detect local recurrence.

Results

Local recurrence appeared in 10 cases after CIRT. Nine of the 10 lesions (90.0 %) were detected with FDG-PET, while enhanced MRI detected just 50.0 % of the recurrences. One case of local recurrence, in which the lesion was negative on FDG-PET, was detected using enhanced MRI. A receiver operating characteristic curve analysis showed that neither the SUVmax on FDG-PET nor the tumor size before or three months after CIRT could be used to predict local recurrence.

Conclusions

The combination of FDG-PET and enhanced MRI is recommended to detect local recurrence for patients with sarcomas who have received CIRT; however, no parameters obtained during the examinations performed before and three months after CIRT accurately predicted the development of local recurrence.

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Adjuvant radiation therapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials- an update

Abstract

Background

Adjuvant radiotherapy (RT) of regional lymph nodes (LN) in early breast cancer is still a matter of debate. RT increases the Overall survival (OS) rate of breast cancer patients after breast conserving surgery and after mastectomy in patients with involved LN. The contribution of RT to regional LN to this improvement was poorly identified. Recently, the results of three large randomized trials addressing this question were published as full papers.

Material and methods

Published data of the MA.20 (n = 1832), the EORTC22922–10925 (EORTC) (n = 4004) trial and the French trial (n = 1334) were the foundation of this meta-analysis. Major eligibility criteria were positive i) axillary LN (all trials), ii) LN negative disease with high risk for recurrence (MA.20), and iii) medial/central tumor location (French, EORTC). The MA.20 and the EORTC trial analyzed the effect of additional regional RT to the internal mammary (IM) LN and medial supraclavicular (MS) LN, whereas in the French trial all patients received RT to the MS-LN and solely RT to the IM-LN was randomized. Primary endpoint was OS. Secondary endpoints were disease-free survival (DFS) and distant metastasis free survival (DMFS).

Results

Regional RT of MS-LN and IM-LN (MA.20 and EORTC) resulted in a significant improvement of OS [Hazard Ratio (HR) 0.88 (95 % CL 0.78 - 0.99)]. Adding results of the French trial and using a random effects model to respect the different design of the French trial, the effect on OS of regional RT remained significant [HR 0.90 (95 % CL 0.82 - 0.99)]. The absolute benefits in OS were 1 % in the MA.20 trial at 10 years, 1.6 % in the EORTC trial at 10 years, and 3.3 % in the French trial at 10 years (not significant in single trials). Regional RT of MS-LN and IM-LN (MA.20 and EORTC) yielded to a significant improvement of DFS [HR 0.86 (95 % CL 0.78 - 0.95)] and DMFS [HR 0.84 (95 % CL 0.75 - 0.94)].

Conclusion

Additional regional RT to the internal mammary and medial supraclavicular LN statistically significantly improved DFS, DMFS, and OS in stage I-III breast cancer.

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MM-398 (nanoliposomal irinotecan): emergence of a novel therapy for the treatment of advanced pancreatic cancer

Future Oncology Ahead of Print.


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Corrigendum

Future Oncology Ahead of Print.


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Corrigendum

Future Oncology January 2016, Vol. 12, No. 2, Pages 272-272.


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Corrigendum

Future Oncology January 2016, Vol. 12, No. 1, Pages 138-138.


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Exposure to maternal smoking during pregnancy and risk of childhood cancer: a study using the Danish national registers

Abstract

Purpose

The relation between maternal smoking during pregnancy and childhood cancer in the offspring remains uncertain. This paper uses Danish national registers, which have collected data prospectively on smoking and cancer, to investigate the association.

Methods

Smoking during pregnancy was ascertained from maternal self-reported data in the Danish National Patient Register. Index children were followed up from birth until the first of the following events: cancer diagnosis, death, emigration, day before 15th birthday, or end of follow-up. Smoking during pregnancy was considered as a binary variable (no smoking in pregnancy and smoking in pregnancy) and by amounts smoked (no smoking, cessation during pregnancy, ≤5, 6–10, or ≥11 cigarettes/day).

Results

Of the 801,867 children included in the study, 20 % were exposed to maternal smoking during pregnancy. Overall, the hazard ratio (HR) for childhood cancer for the exposed compared to the non-exposed was 0.91 [95 % confidence interval (CI) 0.78, 1.07]. Stratification by number of cigarettes also gave statistically nonsignificant inverse associations. There was a statistically significant increased risk of childhood cancer among children whose mothers reported smoking cessation in pregnancy (HR 1.46; 95 % CI 1.01, 2.10). Regarding specific cancer sites, maternal smoking in pregnancy was positively associated with the risk of eye cancers in childhood.

Conclusions

Our results do not provide evidence for an association between maternal smoking in pregnancy and childhood cancer overall. An increased risk of childhood cancer was seen for children whose mothers reported smoking cessation in pregnancy. Future research could employ biomarkers, such as cotinine, to validate maternal smoking status recorded in registers as, even if collected prospectively, this self-reported variable may be subject to reporting bias.

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SEOM clinical guidelines for the treatment of non-small cell lung cancer (NSCLC) 2015

Abstract

Lung cancer is the most common cancer worldwide as well as the leading cause of cancer related deaths as reported by Torre et al (CA Cancer J Clin 65:87–108, 2015]. Non-small cell lung cancer (NSCLC) accounts for up to 85 % of all lung cancers. Multiple advances in the staging, diagnostic procedures, therapeutic options, as well as molecular knowledge have been achieved during the past years, although the overall outlook has not greatly changed for the majority of patients with the overall 5-year survival having marginally increased over the last decade from 15.7 to 17.4 % as reported by Howlader et al.  (SEER Cancer Statistics Review 2015).

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Seom guidelines for the treatment of gastric cancer 2015

Abstract

Gastric cancer is the fourth cause of death by cancer in Spain and a significant medical problem. Molecular biology results evidence that gastroesophageal junction tumors and gastric cancer should be considered as two independent entities with a different prognosis and treatment approach. Endoscopic resection in very early tumors is feasible. Neoadjuvant and adjuvant therapy in locally advanced resectable tumor increase overall survival and should be considered standard treatments. In stage IV tumors, platinum–fluoropyrimidine-based schedule, with trastuzumab in HER2-overexpressed tumors, is the first-line treatment. Different therapies in second line have demonstrated in randomized studies their clear benefit in survival improvement.

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MM-398 (nanoliposomal irinotecan): emergence of a novel therapy for the treatment of advanced pancreatic cancer

Future Oncology Ahead of Print.


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Corrigendum

Future Oncology Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/1kdXdRH
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Corrigendum

Future Oncology January 2016, Vol. 12, No. 2, Pages 272-272.


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Corrigendum

Future Oncology January 2016, Vol. 12, No. 1, Pages 138-138.


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Long-term outcomes of tyrosine kinase inhibitor discontinuation in patients with metastatic renal cell carcinoma

Abstract

Purpose

The purpose of the current study was to evaluate the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) who interrupted vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR–TKI) therapy.

Methods

A retrospective analysis of medical records was performed on all patients with mRCC treated with VEGFR–TKIs between January 2008 and July 2014 (n = 505). Patients who achieved stable disease (SD) or a better response under TKI and later discontinued TKI treatment for any reason with the exception of disease progression were included in the analysis.

Results

We identified 32 patients (sunitinib = 20, sorafenib = 7, and pazopanib = 5). The responses to VEGFR–TKIs were complete response (CR, n = 4), partial response (PR, n = 11), SD (n = 15), and controlled but nonmeasurable response (n = 2). Median time to TKI discontinuation from the initiation of VEGFR–TKI therapy was 16.6 months (95 % CI 12.8–20.3), and the main cause of VEGFR–TKI discontinuation was toxicity (n = 19, 59.4 %). At the time of analysis, 16 patients had disease progression and one patient died. With a median follow-up duration of 51.7 months (range 11.5–87.6), median progression-free survival (PFS) after TKI discontinuation was 20.2 months (95 % CI 6.4–34.0). In multivariate analysis, the duration of TKI therapy (<1 year) before TKI discontinuation was an independent significant prognostic factor of poor PFS (p = 0.045). Among 11 patients who were retreated with the same TKI, two patients (18.2 %) achieved PR and nine achieved SD (81.8 %).

Conclusions

VEGFR–TKI could be interrupted at least temporarily when clinically warranted in patients with mRCC sufficiently controlled by TKIs.

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A pharmacokinetic analysis of cisplatin and 5-fluorouracil in a patient with esophageal cancer on peritoneal dialysis

Abstract

Background

Very little is known about the pharmacokinetics of chemotherapeutic agents in patients also being treated with continuous ambulatory peritoneal dialysis. We sought to evaluate the pharmacokinetics of cisplatin and 5-fluorouracil in plasma and peritoneal dialysate in a patient being treated for esophageal adenocarcinoma.

Methods

A single patient with esophageal adenocarcinoma and on peritoneal dialysis for end-stage renal disease was treated with cisplatin 25 mg/m² on day 1 of weeks 1 and 5 and continuous infusional 5-fluorouracil 1000 mg/m²/day on days 1–4 of weeks 1 and 5 along with daily radiation therapy. Intense plasma and dialysate sampling was performed during the week 5 administration, followed by quantitation of platinum by atomic absorption spectrophotometry and 5-fluorouracil by LC–MS/MS.

Results

Following systemic administration, clearance of ultrafilterable (active) platinum over the first 6 h was 20.8 L/h, which is lower than previously reported clearance levels of ultrafilterable platinum. Total platinum AUC was 131 μg h/mL, also higher than an AUC previously reported for total platinum in patients with normal renal function. Platinum-related material was detected in the peritoneal cavity, but this is likely inactive. 5-Fluorouracil penetrated the intraperitoneal cavity, but the contribution of peritoneal dialysis to drug clearance was negligible at 0.072 %.

Conclusions

Administration of intravenous cisplatin and 5-fluorouracil chemotherapy to a patient treated with continuous ambulatory peritoneal dialysis is feasible, but clearance in dialysate is nominal, thus suggesting that dose reduction is indicated for cisplatin. Systemic drug administration results in limited intraperitoneal penetration of 5-fluorouracil and inactive platinum species.

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Level of Awareness of Various Aspects of Lung Cancer Among College Teachers in India: Impact of Cancer Awareness Programmes in Prevention and Early Detection

Abstract

Lung cancer is one of the most common causes of cancer mortality among men in India and incidence is increasing, but actually, they are largely preventable diseases. In India, advanced stage at the time of presentation is responsible for high mortality and morbidity and early detection is the only way to reduce it. The purpose of this study is to know the level of awareness of various aspects of lung cancer among college teachers and impact of awareness programmes in its prevention and early detection. This assessment was part of Pink Chain Campaign—a campaign on cancer awareness. During the cancer awareness events in 2011–2013 at various women colleges in different parts in India, pre-test related to lung cancer was followed by awareness programme. Post-test using the same questionnaire was conducted at the end of interactive session, at 6 months and 1 year. A total of 872 out of 985 teachers participated in the study (overall response rate was 88.5 %). Mean age of the study population was 41.6 years (range 26–59 years). There was a significant increase in the level of knowledge regarding lung cancer at 6 months, and this was sustained at 1 year. Among teachers who were just asked yes or no question, 117 teachers (13.4 %) were smokers and 241 teachers (27.6 %) were alcoholics. Magazines and newspapers were sources for knowledge in 50–60 % of teachers, whereas approximately 30 % of teachers were educated by TV and Internet regarding various aspects of lung cancer. Post awareness at 6 months and 1 year, Pink Chain Campaign was the major source of knowledge related to lung cancer in more than 90 % of teachers by continuous and timely update on subject. Post awareness at 6 months and 1 year, there was a significant change in alcohol and smoking habits. Major reasons for not going for check-up were ignorance (83.1 %), fear (30.1 %) and lethargic attitude (29.3 %) initially, but over time, lack of time, lethargic attitude and hesitation became important factors after knowing various aspects of lung cancer. Knowledge of lung cancer was very low among teachers. Overall awareness of risk factors, sign and symptoms, screening modalities of lung cancer has improved in a year along with practices related to smoking and alcohol, but there was not much improvement in people undergoing regular check-ups. To inculcate safe practices in the lifestyle of people, awareness programmes such as the Pink Chain Campaign should be conducted more widely and frequently.

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A Qualitative Exploration of Latinos’ Perceptions About Skin Cancer: the Role of Gender and Linguistic Acculturation

Abstract

Latinos have the highest rate of skin cancers among U.S. minorities. Despite a rising incidence of melanoma—the deadliest form of skin cancer—and greater disease burden, Latinos tend to have poor awareness of skin cancer risk factors which may inhibit preventive action. We expanded on prior work by qualitatively examining potential moderators (i.e., gender, acculturation) of skin cancer perceptions among Latinos from El Barrio in Harlem, New York City. Four focus groups stratified by language (English/Spanish) and gender were conducted. Discussions were recorded, transcribed, and coded using thematic analysis. Thirty-eight self-identified Latinos (32 % male) participated. Across groups, median age was 35 years; 50 % completed <high school degree, 82 % had annual incomes ≤$29,999, and 55 % were born in Mexico. Mean acculturation level was 8.5 (SD = 3.9, range = 4–20). Major themes included (1) knowledge of common skin cancer risk factors, (2) acknowledgment of personal risk although lighter-skin individuals are at greater risk, and (3) awareness of effective risk reduction methods, despite the presence of fatalistic beliefs. Compared to males, females discussed tanning norms and appearance-based factors, identified children as vulnerable, highlighted the benefits of sun exposure, and wanted more information. Few linguistic acculturation patterns were noted; English speakers questioned the carcinogenic effect of sunscreen and reported more skin cancer-related physician discussions than Spanish speakers. Despite generally low acculturation, Latinos correctly identified skin cancer risk factors and agreed that it is preventable with engagement in risk-reducing behaviors. Future educational interventions must capitalize upon and reinforce such beliefs and address fatalistic perceptions which may hinder prevention efforts.

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Late Recurrence of Low-Risk Stage II Colorectal Cancer Shortly After Etanercept

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Phase II Study of Capecitabine in Substitution of 5-FU in the Chemoradiotherapy Regimen for Patients with Localized Squamous Cell Carcinoma of the Anal Canal

Abstract

Summary

This was a phase II study of capecitabine in substitution of 5-fluorouracil (5-FU) in the chemoradiotherapy regimen for patients with localized squamous cell carcinoma of the anal canal.

Background

Combined chemoradiation with infusional 5-FU and mitomycin is the standard treatment for localized squamous cell carcinoma (SCC) of the anal canal. Capecitabine is an oral fluoropirimidine that has been shown to be equally effective to 5-FU in many solid tumors. However, the efficacy of the substitution of 5-FU for capecitabine in anal SCC needs confirmation.

Methods

Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status and normal blood and renal function, were treated with capecitabine 825 mg/m² bid during radiotherapy associated with a single dose of mitomycin 15 mg/m² on day 1. The primary objective was local control rate at 6 months determined by clinical examination and radiological assessment. Sample size was calculated using the Fleming single-stage design.

Results

From November 2010 to February 2014, N = 51 patients were initially included; however, 43 patients were assessed. Seventeen patients (39.5 %) were stage II, 11 patients (25.6 %) stage IIIA, and 15 patients (34.9 %) stage IIIB. Four patients (9.3 %) were HIV positive. With a median follow-up of 23.1 months (range 4 to 44.4 months), 3 patients (7 %) presented partial response, 37 (86 %) had complete response, and 3 patients developed progression of the disease (7 %) at 6 months. The colostomy rate was 18.6 %. It was observed a locoregional control of 86 % in 6 months (CI 95 % 0.72–0.94). The main grade 3–4 toxicities were grade 3 radiodermitis in 10 patients (23.2 %), grade 3 lymphopenia in 5 patients (11.6 %), and grade 3 neutropenia in 2 patients (6.9 %). One HIV-positive patient had septic shock, pneumonia, herpetic encephalitis, atrial fibrillation, and macrophage activation syndrome.

Conclusions

Capecitabine can safely substitute infusional 5-FU in the standard chemoradiation regimen for SCC of the anal cancer, with a locoregional control of 86 % in 6 months (CI 95 % 0.72–0.94).

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Self-Expanding Metallic Stents (SEMS) in Left-Sided Colonic Cancer—a Cancer Center Experience

Abstract

Background and Study Aims

Self-Expanding Metallic Stents (SEMS) are a surgery-sparing option for malignant colonic obstruction. They can be inserted as a "bridge to surgery" (BTS) for potentially curable disease, or as a palliative measure, thereby avoiding the higher morbidity and mortality associated with surgery. The objective of this study was to report our local experience of left-sided colonic stents.

Methods

Data on 49 patients was collected retrospectively from Oct 2008 to Nov 2014 at our cancer centre. This included demographics, baseline clinical characteristics, indications for SEMS placement (bridge to surgery/palliative), technical and clinical success, complications, and the mean patency of duration. Survival in both groups was also plotted on a Kaplan-Meier chart.

Results

A total of 49 patients with colorectal carcinoma (CRC) of the left side were enrolled. The mean age was 50 years (range 18–86). Ninety percent of patients had disease involving the rectum, sigmoid colon, or both. Forty-seven percent (n = 23) of patients had stent insertion as a BTS, whereas 53 % (n = 26) had the procedure with palliative intent. Technical and clinical success rates were 96 and 88 %, respectively. The clinical success rate of the palliative arm was lower than that of the BTS arm (p = 0.024). 87.5 % (n = 42) had no procedure-related complications. Technical failure, perforation, and stent migration/expulsion, were each observed in 4 % of cases. Mean stent patency duration was 83.9 days.

Conclusion

SEMS insertion for left-sided malignant colonic obstruction is a safe and effective procedure when used either as a bridge to surgery or with palliative intent.

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Annular dynamics after mitral valve repair with different prosthetic rings: A real-time three-dimensional transesophageal echocardiography study

Abstract

Purpose

We assessed the effects of different types of prosthetic rings on mitral annular dynamics using real-time three-dimensional echocardiography (RT3DE).

Methods

RT3DE was performed in 44 patients, including patients undergoing mitral annuloplasty using the Cosgrove–Edwards flexible band (Group A, n = 10), the semi-rigid Sorin Memo 3D ring (Group B, n = 17), the semi-rigid Edwards Physio II ring (Group C, n = 7) and ten control subjects. Various annular diameters were measured throughout the cardiac cycle.

Results

We observed flexible anterior annulus motion in all of the groups except Group C. A flexible posterior annulus was only observed in Group B and the Control group. The mitral annular area changed during the cardiac cycle by 8.4 ± 3.2, 6.3 ± 2.0, 3.2 ± 1.3, and 11.6 ± 5.0 % in Group A, Group B, Group C, and the Control group, respectively. The dynamic diastolic to systolic change in mitral annular diameters was lost in Group C, while it was maintained in Group A, and to a good degree in Group B. In comparison to the Control group, the mitral annulus shape was more ellipsoid in Group B and Group C, and more circular in Group A.

Conclusion

Although mitral regurgitation was well controlled by all of the types of rings that were utilized in the present study, we demonstrated that the annulus motion and annulus shape differed according to the type of prosthetic ring that was used, which might provide important information for the selection of an appropriate prosthetic ring.

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The numbers games

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The internal acoustic canal - another review area in paediatric sensorineural hearing loss

Abstract

Morphological abnormalities of the internal acoustic canal (IAC), albeit rare, are sometimes associated with hearing loss in children. We present an illustration of the spectrum of IAC abnormalities together with a brief review of the embryology and anatomy of the IAC and the techniques used when imaging the petrous temporal bone. This review focuses on morphological abnormalities of the IAC together with their clinical implications and impact on clinical management.

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Hypoplastic left heart syndrome and the nutmeg lung pattern in utero: a cause and effect relationship or prognostic indicator?

Abstract

Background

Hypoplastic left heart syndrome (HLHS) is the third most common cause of critical congenital heart disease in newborns, and one of the most challenging forms to treat. Secondary pulmonary lymphangiectasia has been recognized in association with HLHS, an appearance described on fetal MRI as the "nutmeg lung."

Objective

To investigate the association of fetal nutmeg lung with HLHS survival.

Materials and methods

A retrospective search of the fetal MRI database was performed. The nutmeg lung pattern was defined as T2 heterogeneous signal with tubular structures radiating peripherally from the hila. Postnatal echocardiograms and charts were reviewed.

Results

Forty-four fetal MR studies met inclusion criteria, of which 4 patients (9%) had the nutmeg lung pattern and 3 of whom also had restrictive lesions. Mortality in this nutmeg lung group was 100% by 5 months of age. Of the 40 patients without nutmeg lung, mortality/orthotopic heart transplant (OHT) was 35%. Of these 40 patients without nutmeg lung, 5 had restriction on echo, 3 of whom died/had OHT before 5 months of age (60% of patients with restriction and non-nutmeg lung). There was a significantly higher incidence of restrictive lesions (P = 0.02) and mortality/OHT (P = 0.02) in patients with nutmeg lung compared to those without.

Conclusion

The nutmeg lung MR appearance in HLHS fetuses is associated with increased mortality/OHT (100% in the first 5 months of life compared to 35% with HLHS alone). Not all patients with restrictive lesions develop nutmeg lung, and outcome is not as poor when restriction is present in isolation. Dedicated evaluation for nutmeg lung pattern on fetal MR studies may be useful to guide prognostication and aid clinicians in counseling parents of fetuses with HLHS.

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Targeting STAT3/miR-21 axis inhibits epithelial-mesenchymal transition via regulating CDK5 in head and neck squamous cell carcinoma

Abstract

Background

Abnormal activation of STAT3 and miR-21 plays a vital role in progression and invasion of solid tumors. The cyclin-dependent kinase 5 (CDK5) is reported to contribute to cancer metastasis by regulating epithelial-mesenchymal transition (EMT). However, the role of STAT3/miR-21 axis and CDK5 in head and neck squamous cell carcinoma remains unclear.

Methods

We measured the expression of miR-21, CDK5 and EMT markers in 60 HNSCC tumor samples. We used Immunohistochemistry and in situ hybridization assay to examine the role of STAT3/miR-21 axis and CDK5 activation in the invasiveness of HNSCC. The clinical survival relevance was analyzed by Kaplan-Meier analysis and univariate/multivariate COX regression model. Multiple approaches including scratch, transwell chamber assay and other molecular biology techniques were used to validate the anti-invasion effect of targeting miR-21 in Tca8113 and Hep-2 cell lines in vitro. Furthermore, whether miR-21 depletion inhibits HNSCC invasion in vivo was confirmed in Tca8113 xenograft tumor model.

Results

The expression of miR-21 and CDK5 were significantly correlated with lymph node metastasis in HNSCC. Hep-2 and Tca8113 cell lines showed co-overexpression of miR-21 and CDK5. WP1066 or asON-miR-21 treatment depleted miR-21 and CDK5 expression and significantly inhibited migration or invasion in Hep-2 and Tca8113 cells. The expression levels of CDK5/p35, N-cadherin, vimentin, β-catenin were inhibited while E-cadherin level was increased by miR-21 depletion in vitro and in vivo. Conversely, ectopic CDK5 overexpression significantly induced tumor cell motility and EMT. Moreover, ectopic CDK5 overexpression in Hep-2 and Tca8113 cells rescued the observed phenotype after miR-21 silencing or WP1066 treatment.

Conclusions

miR-21 cooperates with CDK5 to promote EMT and invasion in HNSCC. This finding suggests that CDK5 may be an important cofactor for targeting when designing metastasis-blocking therapy by targeting STAT3/miR-21 axis with STAT3 inhibitor or miR-21 antisense oligonucleotide. This is the first demonstration of the novel role of STAT3/miR-21 axis and CDK5/CDK5R1 (p35) in metastasis of HNSCC.

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Is there evidence for a better health care for cancer patients after a second opinion? A systematic review

Abstract

Background

With growing complexity of diagnostics and therapy, as well as increasing involvement of patients in the decision-making process, there is more and more demand for second opinions in oncology. This literature review aims at analyzing the benefits and risks involved, as well as the tools needed to establish a structured program for second opinion within a modern healthcare system.

Methods

A systematic literature search was performed using MEDLINE and Embase and the databases SocINDEX, ERIC and CINAHL. Thirteen articles met the inclusion criteria and offered a relevant insight into the topic of second opinions.

Results

Depending on the study, between 6.5 and 36 % of patients search for a second opinion, due to a variety of reasons. Changes in diagnosis, treatment recommendations or prognosis as a result of the second opinion occurred in 12–69 % of cases. In 43–82 % of cases, the original diagnosis or treatment was verified. Patient satisfaction was high, and the second opinion was deemed as helpful and reassuring in most cases. Yet, data on patient-relevant outcomes or on the quality of the second opinion are missing.

Conclusion

In general, outcome data on second opinion are divergent and scarce. Yet, with patients' demand for second opinion and influence of second opinion on treatment decisions, a structured, high quality and transparent second-opinion program seems mandatory. Such a program may support patient–physician communication and improve the flow of information, as well as decision-making. Its evaluation should be independent from the provider of the second opinion.

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Effect of Selenium Supplementation on Glycemic Control and Lipid Profiles in Patients with Diabetic Nephropathy

Abstract

To our knowledge, data on the effects of selenium supplementation on glycemic control and lipid concentrations in patients with diabetic nephropathy (DN) are scarce. The current study was done to determine the effects of selenium supplementation on glycemic control and lipid concentrations in patients with DN. This was a randomized double-blind placebo-controlled clinical trial in which 60 patients with DN were randomly allocated into two groups to receive either 200 μg of selenium supplements (n = 30) or placebo (n = 30) daily for 12 weeks. Blood sampling was performed for the quantification of glycemic indicators and lipid profiles at the onset of the study and after 12 weeks of intervention. Selenium supplementation for 12 weeks resulted in a significant decrease in serum insulin levels (P = 0.01), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), homeostasis model of assessment-estimated B cell function (HOMA-B) (P = 0.009) and a significant rise in plasma glutathione peroxidase (GPx) (P = 0.001) compared with the placebo. Taking selenium supplements had no significant effects on fasting plasma glucose (FPG), quantitative insulin sensitivity check index (QUICKI) and lipid profiles compared with the placebo. Overall, our study demonstrated that selenium supplementation for 12 weeks among patients with DN had beneficial effects on plasma GPx, serum insulin levels, HOMA-IR, and HOMA-B, while it did not affect FPG, QUICKI, and lipid profiles.

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Calcium Fructoborate for Bone and Cardiovascular Health

Abstract

Calcium fructoborate (CF), a natural sugar-borate ester found in fresh fruits and vegetables, is a source of soluble boron. CF contains three forms of borate (diester, monoester, and boric acid) and all are biologically active, both at the intracellular (as free boric acid) and extracellular level (as fructose-borate diester and monoester). At the cellular and molecular level, CF is superior to the boric acid/borate, exhibiting a complex "protective" effect against inflammatory response. CF is commercially available in the USA as a "nature-identical" complex, an active compound for dietary supplements. It provides effective and safe support against the discomfort and lack of flexibility associated with osteoarticular conditions (arthritis and joint degeneration), and improves Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and McGill indexes. In addition, orally administered CF is effective in ameliorating symptoms of physiological response to stress, including inflammation of the mucous membranes, discomfort associated with osteoarthritis disorders, and bone loss, and also for supporting cardiovascular health. Clinical studies have exhibited the ability of CF to significantly modulate molecular markers associated with inflammatory mechanisms, mainly on the elevated serum levels of C-reactive protein (CRP).

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Clinical evaluation of the effects of supplementation with curcuminoids on serum fetuin-B concentrations in obese subjects

Abstract

Fetuin-B is an emerging negative acute phase protein, and its expression is inversely associated with inflammation. The present study aimed to assess the impact of supplementation with curcuminoids, as naturally occurring polyphenols with anti-inflammatory properties, on circulating concentrations of fetuin-B. In this randomized double-blind trial, 30 obese dyslipidemic subjects received curcuminoids (1 g/day) and matching placebo. The trial had a 2 × 2 crossover design, in which treatment duration with either of the allocations was 4 weeks, intermitted by a 2-week washout period. Serum fetuin-B concentrations were determined at the end of each treatment period. The groups were comparable regarding baseline demographic characteristics and serum fetuin-B concentrations. Supplementation with curcuminoids did not significantly change serum fetuin-B levels compared with placebo (p > 0.05). Serum fetuin-B levels were not found to be correlated with lipid profile parameters nor C-reactive protein in either curcuminoids or placebo groups (p > 0.05). Four-week supplementation with curcuminoids in obese subjects has no significant effect on circulating fetuin-B concentrations.

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Trypanosoma vivax infection in goat in west of Santa Catarina state, Brazil

Abstract

The aim of this study was to report the Trypanosoma vivax in goats from a property located in the west of the state of Santa Catarina, Brazil. The identification of the parasite occurred at random, that is, it was displayed a similar morphological trypomastigote form in the blood smear of an animal in the property. Subsequently, in blood samples collected from five goats on the same day, it was confirmed by polymerase chain reaction (PCR) the presence of the parasite in three of these animals. Being that by chance, consistent clinical signs related to trypanosomosis in these animals were not observed. The animals were not subjected to therapeutic treatment, because the molecular confirmation of the parasitism happened 1.4 years after the sample collection. Therefore, the T. vivax parasite infects goats in the state of Santa Catarina, Brazil.

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Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the βIII isotype of tubulin

Summary

The subunit protein of microtubules is tubulin, which has been the target for some of the most successful and widely used anti-tumor drugs. Most of the drugs that target tubulin bind to the β subunit. There are many isotypes of β-tubulin and their distributions differ among different tissues. The βIII isotype is over-expressed in many tumors, particularly those that are aggressive, metastatic, and drug resistant. We have previously reported the design and synthesis of a series of compounds to fit the colchicine site on βIII but not on the other isotypes. In the current study, we tested the toxicity and the anti-tumor activity of one of these compounds, CH-35, on the human breast tumor MDA-MB-231 over-expressing βIII in a xenogeneic mouse model. We found that CH-35 was as toxic as Taxol® in vivo. Although the βIII-over-expressing cells developed into very fast-growing tumors, CH-35 was more effective against this tumor than was Taxol. Our results suggest that CH-35 is a promising candidate for future drug development.

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The atypical urothelial cell category in the Paris System: Strengthening the Achilles' heel

The category of atypical urothelial cell has to date been an equivocal diagnostic category, causing frustration to both cytopathologists and clinicians. The new Paris System for Reporting Urinary Cytology now offers well-defined criteria that will help to standardize this problematic category as well as gather meaningful, comparable follow-up data from diverse institutions.

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Sexual health problems in French cancer survivors 2 years after diagnosis—the national VICAN survey

Abstract

Purpose

The purpose of this study is to assess French cancer survivors' sexual health 2 years after diagnosis.

Methods

Using the French National Health Insurance System database, the representative national VICAN survey was created comprising 4349 adults (12 cancer sites), still alive 2 years after diagnosis and aged 18–52 ("younger") or 53–82 ("older"). Sexual health was evaluated using six items from the Relationship and Sexuality Scale, and an overall indicator was created.

Results

Among the study's 1955 sexually active participants, 18.6 % (versus 13.1 %), 39.8 % (versus 39.9 %) and 29.4 % (versus 29.8 %) of men (versus women) were affected, respectively, by "strong", "moderate" and "weak" sexual health deterioration, while 12.2 % (versus 17.1 %) were spared sexual problems (P = 0.001). Strong deterioration more often concerned older men with prostate (27.7 %) and lung (26.1 %) cancers, younger men with upper aero-digestive tract cancers (25.2 %) and women (younger/older) with cervical cancer (24.2 %). Substantial (strong/moderate) sexual health deterioration was observed for all cancer sites, rates ranging from 68.3 % (prostate) to 37.2 % (melanoma). In all four gender/age subgroups, increasing age predicted poorer sexual health, although statistical significance was not reached in older women. Apart from genital cancer, perceived consequences, such as general sequelae and fatigue, were the primary factors associated with severe sexual problems.

Conclusions

Two years after diagnosis, the majority of sexually active French cancer survivors reported impaired sexual health. Younger and older men and women with cancer in non-reproductive sites also reported problems.

Implications for Cancer Survivors

Interventions aimed at improving sexual health irrespective of age and cancer site should be developed.

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The emerging role of Snail1 in the tumor stroma

Abstract

The transcription factor Snail1 leads to the epithelial–mesenchymal transition by repressing the adherent and tight junctions in epithelial cells. This process is related to an increase of cell migratory and mesenchymal properties during both embryonic development and tumor progression. Although Snail1 expression is very limited in adult animals, emerging evidence has placed Snail at the forefront of medical science. As a transcriptional repressor, Snail1 confers cancer stem cell-like traits on tumor cells and promotes drug resistance, tumor recurrence and metastasis. In this review, we summarize recent reports that suggest the pro-tumorigenic roles of Snail1 expression in tumor stroma. The crosstalk between tumor and stromal cells mediated by Snail1 regulates paracrine communication, pro-tumorigenic abilities of cancer cells, extracellular matrix characteristics and mesenchymal differentiation in cancer stem cells and cancer-associated fibroblasts. Therefore, understanding the regulation and functional roles of Snail1 in the tumor microenvironment will provide us with new therapies for treating metastatic disease.

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CancerNet: a database for decoding multilevel molecular interactions across diverse cancer types

CancerNet: a database for decoding multilevel molecular interactions across diverse cancer types

Oncogenesis 4, e177 (December 2015). doi:10.1038/oncsis.2015.40

Authors: X Meng, J Wang, C Yuan, X Li, Y Zhou, R Hofestädt & M Chen

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Chloroquine alleviates etoposide-induced centrosome amplification by inhibiting CDK2 in adrenocortical tumor cells

Chloroquine alleviates etoposide-induced centrosome amplification by inhibiting CDK2 in adrenocortical tumor cells

Oncogenesis 4, e180 (December 2015). doi:10.1038/oncsis.2015.37

Authors: T-Y Chen, J-S Syu, T-C Lin, H-l Cheng, F-l Lu & C-Y Wang

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MN1–Fli1 oncofusion transforms murine hematopoietic progenitor cells into acute megakaryoblastic leukemia cells

MN1–Fli1 oncofusion transforms murine hematopoietic progenitor cells into acute megakaryoblastic leukemia cells

Oncogenesis 4, e179 (December 2015). doi:10.1038/oncsis.2015.41

Authors: D V Wenge, E Felipe-Fumero, L Angenendt, C Schliemann, E Schmidt, L H Schmidt, C Thiede, G Ehninger, W E Berdel, M-F Arteaga & J-H Mikesch

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Psychosocial oncology care resources in Europe: a study under the European Partnership for Action Against Cancer (EPAAC)

Abstract

Background

Cancer is a complex health problem requiring multidisciplinary care. There are clinical guidelines available in order to improve the process and outcomes of cancer care within Europe. However, strategic action is still needed in many European Union (EU) Member States to develop or improve national cancer control plans (NCCPs), which play a key role in cancer control and care. The current study clarifies the extent of implementation of psychosocial oncology care (PSOC) in the EU.

Method

A survey methodology was used to cover four dimensions: (1) inclusion of PSOC in NCCPs; (2) structure and resources of PSOC delivery; (3) use of NCCP clinical guidelines; and (4) education and training resources available along with determination of training needs in PSOC.

Results

Twenty-seven (90%) countries returned questionnaires of which 21 (78%) include PSOC in their NCCP. However, only 10 (37%) reported having specific budgets for PSOC, 8 (30%) having nationally recommended PSOC clinical guidelines, and 6 countries (22%) reported having an official certification for PSOC education.

Conclusion

Although many countries seem to have integrated PSOC into their NCCP, there is still much to do in terms of allocating resources and delivering psychosocial care equitably. Also, there is a need for improving training and certification in PSOC. The findings indicate the need to develop national policies concerning PSOC with clear targets for deliverables in an appropriate timetable in order that psychosocial services and existing clinical guidelines are implemented and fully integrated into EU NCCPs. Copyright © 2015 John Wiley & Sons, Ltd.

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The clinicopathological significance of NAB2-STAT6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors

Abstract

NAB2-STAT6 gene fusion drives STAT6 nuclear expression and is the pathognomonic hallmark of solitary fibrous tumors (SFTs). However, no study has systematically analyzed the clinicopathological features, STAT6 immunoexpression status, or the fusion variants of NAB2-STAT6 in intrathoracic SFTs. Fifty-two intrathoracic SFTs were retrieved to appraise histopathology, assess STAT6 immunoexpression, and determine NAB2-STAT6 fusion variants by RT-PCR. Location-relevant histologic mimics served as controls. Thirty-one pleura-based, 12 mediastinal/pericardial, and nine intrapulmonary lesions were histologically categorized into eight malignant, eight atypical, and 36 conventional or cellular SFTs, including two fat-forming and two giant cell angiofibroma-like SFTs. STAT6 distinctively decorated the tumoral nuclei in 51 (98%) SFTs. However, no nuclear staining was observed in the histological mimics. NAB2-STAT6 fusion was detected in 34 SFTs. Twenty-nine (85.3%) exhibited the major NAB2ex4-STAT6ex2/3 variant and 5 (14.7%) the minor NAB2ex6-STAT6ex16/17. NAB2ex4-STAT6ex2 was significantly associated with older age (P = 0.01) and pleuropulmonary tumors (P = 0.025). After a median follow-up of 33.9 (range, 0.3–174.6) months, adverse outcomes occurred in one atypical and five malignant SFTs, including two local relapses, one intrapulmonary metastasis, and three extrathoracic metastases. Inferior disease-free survival was univariately associated with atypical/malignant histology (P = 0.001) and a mitosis >4/10 HPFs (P = 0.0012) but was unrelated to fusion variants. In conclusion, the majority of intrathoracic SFTs exhibited STAT6 nuclear staining, and NAB2ex4-STAT6ex2/3 was the predominant fusion type. However, clinical aggressiveness is associated with atypical/malignant histology primarily contributed by increased mitosis but was unrelated to the NAB2-STAT6 fusion variants.

NAB2-STAT6 fusions and nuclear STAT6 expression existed in almost all intrathoracic solitary fibrous tumors, suggesting a common tumorigenesis and a potential therapeutic target. Histologic classification and mitotic figures conferred the prognostic relevance instead of fusion variants.

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Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification

Abstract

Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation-dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5–8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC.

Multiplex ligation-dependent probe amplification is a simple and efficient method for analysis of genomic deletions and duplications in all 12 exons of TP53.

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The effect of aloe emodin–encapsulated nanoliposome-mediated r-caspase-3 gene transfection and photodynamic therapy on human gastric cancer cells

Abstract

Gastric carcinoma (GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy (PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin (AE)–encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer (PS). AE-encapsulated nanoliposomes (nano-AE) were prepared by reverse evaporation method. Electron microscopy and nano-ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase-3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species (ROS) contents were measured by DCFH-DA staining. Outcomes demonstrated that the nano-AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r-caspase-3 was transfected had higher protein expression of the caspase-3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano-AE-mediated PDT in an energy-dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm²). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano-AE PDT group had quadrupled in SGC-7901 cells as early as 1 h after PDT, while it is similar to the group of nano-AE transfection and PDT. Nano-AE-mediated r-caspase-3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human gastric cancer cells.

We first prepared the aloe emodin–encapsulated nanoliposomes (nano-AE), which demonstrated good characteristics of photosensitizer as well as one gene carrier. As shown in our article, nano-AE-mediated r-caspase-3 gene transfection and PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human gastric cancer cells.

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Characteristics of cultured desmoid cells with different CTNNB1 mutation status

Abstract

Desmoid tumors are benign mesenchymal neoplasms with a locally aggressive nature. The mutational status of β-catenin gene (CTNNB1) is presumed to affect the tumorous activity of the cells. In this study, we isolated three kinds of desmoid cell with different CTNNB1 status, and compared their characteristics. Cells were isolated from three patients with abdominal wall desmoid during surgery, all of which were resistant to meloxicam treatment. The mutational status of the CTNNB1 exon 3 was determined for both parental tumor tissues and isolated cultured cells. β-catenin expression was determined with immunohistochemistry. Responsiveness to meloxicam was investigated with MTS assay together with COX-2 immunostaining. mRNA expressions of downstream molecules of Wnt/β-catenin pathway were determined with real-time RT-PCR. Three kinds of cell isolated from desmoid tumors harboring different CTNNB1 mutation status (wild type, T41A, and S45F), all exhibited a spindle shape. These isolated cells could be cultured until the 20th passage with unchanged proliferative activity. Nuclear accumulation of β-catenin was observed in all cultured cells, particularly in those with S45F. Proliferating activity was significantly suppressed by meloxicam (25 μmol/L, P < 0.007) in all three cell cultures, of which parental desmoid was resistant to meloxicam clinically. The mRNA expressions of Axin2, c-Myc, and Cyclin D1 differently increased in the three cultured cell types as compared with those in human skin fibroblast cells (HDF). Inhibitors of Wnt/β-catenin pathway downregulated Axin2, c-Myc, and Cyclin D1 significantly. Isolated and cultured desmoid tumor cells harboring any one of the CTNNB1 mutation status had unique characteristics, and could be useful to investigate desmoid tumors with different mutation status of CTNNB1.

We have successfully isolated and characterized three kinds of desmoid cell with different CTNNB1 status. Isolated and cultured desmoid tumor cells harboring any one of the CTNNB1 mutation status had unique characteristics, and could be useful to investigate desmoid tumors with different mutation status of CTNNB1.

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The benefits of cancer screening in kidney transplant recipients: a single-center experience

Abstract

The frequency of malignancy is increasing in kidney transplant recipients. Posttransplant malignancy (PTM) is a major cause of long-term graft survival inhibition. In this study, we evaluated the frequency and prognosis of PTM at our center and examined the efficacy of cancer screening. Between 1972 and 2013, 750 patients were followed-up at our center. Annual physical examinations and screenings were performed to detect PTM. We investigated the detail of two distinctive cancer groups: screening-detected cancers and symptom-detected cancers. Seventy-seven PTM were identified during the follow-up period. The mean age at the initial PTM detection was 43.6 ± 12.8 years. The mean interval from transplantation to cancer diagnosis was 134.5 ± 11.3 months. Among the 77 patients, posttransplant lymphoproliferative disease (PTLD) was the most common cancer (19.5%, 15/77), followed by renal cell carcinoma (15.6%, 12/77). Of the cancer cases, 46.8% (36/77) were detected via screening. The most frequently screening-detected cancer was renal cell carcinoma of the native kidney and breast cancer (22.2%, 8/36). However, it was difficult to detect PTLD, urothelial carcinoma, and colorectal cancer via screening. Interestingly, Cox proportional regression analyses revealed nonscreened recipients to be a significant prognostic factor for PTM (P < 0.001). This study is the first to report that appropriate screening tests play a key role in early PTM diagnosis and lead to reduce the mortality rate in kidney transplant recipients. These findings support the provision of long-term appropriate screening for kidney transplant recipients.

The authors for the first time found that noncancer screening was a significant prognostic factor for posttransplant malignancy. These findings remind clinical physicians of the importance of early posttransplant malignancy diagnosis via cancer screening.

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Xanthine oxidoreductase in cancer: more than a differentiation marker

Abstract

Human xanthine oxidoreductase (XOR) catalyzes the last two steps of purine catabolism and is present in two interconvertible forms, which may utilize O₂ or NAD⁺ as electron acceptors. In addition to uric acid, XOR products may comprise reactive oxygen and nitrogen species that have many biologic effects, including inflammation, endothelial dysfunction, and cytotoxicity, as well as mutagenesis and induction of proliferation. XOR is strictly modulated at the transcriptional and post-translational levels, and its expression and activity are highly variable in cancer. Xanthine oxidoreductase (XOR) expression has been negatively associated with a high malignity grade and a worse prognosis in neoplasms of the breast, liver, gastrointestinal tract, and kidney, which normally express a high level of XOR protein. However, the level of XOR expression may be associated with a worse outcome in cancer of low XOR-expressing cells, in relation to the inflammatory response elicited through the tissue damage induced by tumor growth. Xanthine oxidoreductase (XOR) has been implicated in the process of oncogenesis either directly because it is able to catalyze the metabolic activation of carcinogenic substances or indirectly through the action of XOR-derived reactive oxygen and nitrogen species. The role of uric acid is characterized by both oxidant and antioxidant action; thus, it is still debatable whether control of uricemia may be helpful to improve the outcomes of tumor illness.

Xanthine oxidoreductase (XOR) activity precludes the salvage pathway of purine nucleotides and may oxidize anticancer drugs and carcinogen substances. In cancer, XOR is upregulated in low-, and downregulated in high-, XOR-expressing tissues. XOR-derived reactive oxygen (ROS) and nitrogen (RNS) species are implicated in oncogenesis because they may induce inflammation, mutagenesis, and proliferation.

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Lymphovascular space invasion and lack of downstaging after neoadjuvant chemotherapy are strong predictors of adverse outcome in young women with locally advanced breast cancer

Abstract

Younger age diagnosis of breast cancer is a predictor of adverse outcome. Here, we evaluate prognostic factors in young women with locally advanced breast cancer (LABC). We present a retrospective review of 104 patients younger than 40 years with LABC treated with surgery, radiotherapy (RT), and chemotherapy from 2003 to 2014. Patient-, tumor-, and treatment-related factors important for overall survival (OS), local/regional recurrence (LRR), distant metastasis (DM), and recurrence-free survival (RFS) were evaluated. Mean age at diagnosis was 34 years (23–39 years) with a median follow-up of 47 months (8–138 months). Breast-conserving surgery was performed in 27%. Axillary lymph node dissection was performed in 85%. Sixty percent of patients received neoadjuvant chemotherapy with 19% achieving pathologic complete response (pCR), and 61% downstaged. Lymph node positivity was present in 91% and lymphovascular space invasion (LVSI) in 35%. Thirty-two percent of patients had triple negative tumors (TN, ER-/PR-/HER2 nonamplified). Four-year OS and RFS was 84% and 71%, respectively. Factors associated with worse OS on multivariate analysis include TN status, LVSI, and number of positive lymph nodes. LVSI was also associated with DM and LRR, as well as worse RFS. Downstaging was associated with improved 4 year RFS in patients receiving neoadjuvant chemotherapy (74% vs. 38%, P = 0.002). With high risks of recurrence and inferior OS compared to older women, breast cancer in young women can be difficult to treat. Among additional factors, presence of LVSI and lack of downstaging portends a particularly worse prognosis.

With high risks of recurrence and inferior overall survival compared to older women, breast cancer in young women can be difficult to treat. Among additional factors, presence of locally advanced breast cancer portends a particularly worse prognosis for all outcomes measured.

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