The relationship between circulating 25-hydroxyvitamin D and survival in newly diagnosed advanced non-small-cell lung cancer

Abstract

Background

Serum 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D used for evaluating the vitamin D status of patients, has been associated with survival in a variety of cancers with conflicting evidence. We aimed to investigate this association in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients.

Methods

This was a consecutive cohort of 359 newly diagnosed stages III-IV NSCLC patients who underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at our institution between January 2008 and December 2010. We used the vitamin D categories of "deficient (<20 ng/ml)" and "not deficient (> = 20 ng/ml)". Cox regression was used to evaluate the prognostic significance of serum 25(OH)D after adjusting for relevant confounders.

Results

Mean age at diagnosis was 57.4 years. Of the 359 patients, 151 (42.1 %) were deficient in vitamin D at the time of diagnosis. The median survival in deficient and not deficient cohorts was 11.7 and 12.8 months respectively (p = 0.06). Season of diagnosis, performance status, smoking status and hospital location significantly predicted vitamin D status. On univariate Cox analysis, gender, stage of disease, hospital location, histologic subtype, subjective global assessment (SGA), performance status, smoking status, body mass index and serum albumin were significantly associated with survival (p <0.05 for all). On multivariate Cox analysis, six variables demonstrated statistically significant associations with survival: stage of disease, hospital location, histologic subtype, SGA, smoking status and serum albumin (p <0.05 for all). Serum vitamin D, which was borderline significant in univariate analysis, lost its significance in multivariate analysis.

Conclusions

We found season of diagnosis, performance status and smoking history to be predictive of vitamin D status. Consistent with previously published research in advanced NSCLC, we did not find any significant association between pre-treatment serum 25(OH)D and survival in our patients.

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Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation

Abstract

Background

Tumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105⁺ CSCs) able to release extracellular vesicles (EVs) that favor tumor progression and metastases. The aim of the present study was to compare the ability of renal CSCs and derived EVs to modulate the behavior of monocyte-derived DCs with a non-tumor initiating renal cancer cell population (CD105^- TCs) and their EVs.

Methods

Maturation of monocyte-derived DCs was studied in presence of CD105⁺ CSCs and CD105^- TCs and their derived EVs. DC differentiation experiments were evaluated by cytofluorimetric analysis. T cell proliferation and ELISA assays were performed. Monocytes and T cells were purified from peripheral blood mononuclear cells obtained from healthy donors.

Results

The results obtained demonstrate that both CD105⁺ CSCs and CD105^- TCs impaired the differentiation process of DCs from monocytes. However, the immune-modulatory effect of CD105⁺ CSCs was significantly greater than that of CD105^- TCs. EVs derived from CD105⁺ CSCs and in less extent, those derived from CD105^- TCs retained the ability to impair monocyte maturation and T cell activation. The mechanism has been mainly related to the expression of HLA-G by tumor cells and to its release in a form associated to EVs. HLA-G blockade significantly reduced the inhibitory effect of EVs on DC differentiation.

Conclusions

In conclusion, the results of the present study indicate that renal cancer cells and in particular CSCs and derived EVs impair maturation of DCs and T cell immune response by a mechanism involving HLA-G.

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A case study on the potential angiogenic effect of human chorionic gonadotropin hormone in rapid progression and spontaneous regression of metastatic renal cell carcinoma during pregnancy and after surgical abortion

Abstract

Background

Treatment possibilities of metastatic renal cell carcinoma (mRCC) have recently changed dramatically prolonging the overall survival of the patients. This kind of development brings new challenges for the care of mRCC.

Case presentation

A 22 year-old female patient with translocation type mRCC, who previously had been treated for nearly 5 years, became pregnant during the treatment break period. Follow-up examinations revealed a dramatic clinical and radiological progression of mRCC in a few weeks therefore the pregnancy was terminated. A few days after surgical abortion, CT examination showed a significant spontaneous regression of the pulmonary metastases, and the volume of the largest manifestation decreased from ca. 30 to 3.5 cm³ in a week. To understand the possible mechanism of this spectacular regression, estrogen, progesterone and luteinizing hormone receptors (ER, PGR and LHR, respectively) immuno-histochemistry assays were performed on the original surgery samples. Immuno-histochemistry showed negative ER, PGR and positive LHR status suggesting the possible angiogenic effect of human chorionic gonadotropin hormone (hCG) in the background.

Conclusion

We hypothesize that pregnancy may play a causal role in the progression of mRCC via the excess amount of hCG, however, more data are necessary to validate the present notions and the predictive role of LHR overexpression.

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Natural killer (NK) cells inhibit systemic metastasis of glioblastoma cells and have therapeutic effects against glioblastomas in the brain

Abstract

Background

Glioblastoma multiforme (GBM) is characterized by extensive local invasion, which is in contrast with extremely rare systemic metastasis of GBM. Molecular mechanisms inhibiting systemic metastasis of GBM would be a novel therapeutic candidate for GBM in the brain.

Methods

Patient-derived GBM cells were primarily cultured from surgical samples of GBM patients and were inoculated into the brains of immune deficient BALB/c-nude or NOD-SCID IL2Rgamma^null (NSG) mice. Human NK cells were isolated from peripheral blood mononucleated cells and expanded in vitro.

Results

Patient-derived GBM cells in the brains of NSG mice unexpectedly induced spontaneous lung metastasis although no metastasis was detected in BALB/c-nude mice. Based on the difference of the innate immunity between two mouse strains, NK cell activities of orthotopic GBM xenograft models based on BALB/c-nude mice were inhibited. NK cell inactivation induced spontaneous lung metastasis of GBM cells, which indicated that NK cells inhibit the systemic metastasis. In vitro cytotoxic activities of human NK cells against GBM cells indicated that cytotoxic activity of NK cells against GBM cells prevents systemic metastasis of GBM and that NK cells could be effective cell therapeutics against GBM. Accordingly, NK cells transplanted into orthotopic GBM xenograft models intravenously or intratumorally induced apoptosis of GBM cells in the brain and showed significant therapeutic effects.

Conclusions

Our results suggest that innate NK immunity is responsible for rare systemic metastasis of GBM and that sufficient supplementation of NK cells could be a promising immunotherapeutic strategy for GBM in the brain.

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TGFβ isoforms and receptors mRNA expression in breast tumours: prognostic value and clinical implications

Abstract

Background

Transforming growth factor beta (TGFβ) signalling is involved in both tumour suppression and tumour progression. The mRNA expression levels of the TGFβ isoforms and receptors in breast tumours may have prognostic value and clinical implications.

Methods

The mRNA levels of TGFB1, TGFB2, TGFB3, TGFBR1 and TGFBR2 were analysed in primary breast tumours and adjacent normal breast tissues, and the associations with tumour characteristics and patients' overall and relapse-free survival were evaluated, using the public gene expression microarray data from The Cancer Genome Atlas (n = 520) and the Gene Expression Omnibus (four datasets) and our quantitative real-time PCR validation data (n = 71).

Results

Significantly higher TGFB1 and TGFB3 mRNA levels and lower TGFBR2 mRNA levels were observed in primary tumours compared with their paired normal tissues. TGFB1 mRNA expression was seemly lower in triple-negative tumours and in tumours from lymph node-negative patients. TGFB3 mRNA expression was significantly lower in estrogen receptor-negative/progesterone receptor-negative/Basal-like/Grade 3 tumours. High TGFB2, TGFB3 and TGFBR2 mRNA levels in tumours were generally associated with better prognosis for patients, especially those diagnosed with lymph node-negative diseases. High TGFBR1 mRNA levels in tumours were associated with poorer clinical outcomes for patients diagnosed with small (diameter ≤2 cm) tumours.

Conclusions

The results indicate a reduced responsiveness of tumour cells to TGFβ, a preferential up-regulation of TGFB1 in malignant tumours and a preferential up-regulation of TGFB3 in premalignant tumours. The results may not only provide prognostic value for patients but also assist in classifying tumours according to their potential responses to TGFβ and selecting patients for TGFβ signalling pathway targeted therapies.

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Enormous, rapidly growing breast mass

Abstract

Background

Signs and symptoms of a rapidly enlarging breast mass are not only important for all clinicians to recognize and assess, but also are not uncommon occurrences. We describe a similar but unique case that developed into an enormous, 36 cm exophytic mass.

Case presentation

A 51-year-old woman with history of psychiatric conditions presented for signs and symptoms of sepsis. It was determined that the source was an enormous 36 cm mass originating from the breast/chest wall. After stabilizing the patient with antibiotics, she underwent successful resection. Surgical margins were positive, and histopathology demonstrated bland spindle cells with stromal overgrowth. Together with clinical and histopathological information, the patient was diagnosed with a phyllodes tumor.

Conclusion

Differential diagnosis of rapidly growing breast masses is discussed, which are not uncommon occurrences in clinical medicine. One etiology, phyllodes tumors, can grow into large, exophytic masses as described. Oncologic treatment is discussed, usually consisting of surgery with postoperative radiotherapy for high-risk features.

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Annual Medical Expenditure and Productivity Loss Among Colorectal, Female Breast, and Prostate Cancer Survivors in the United States

Background:

There are limited nationally representative estimates of the annual economic burden among survivors of the three most prevalent cancers (colorectal, female breast, and prostate) in both nonelderly and elderly populations in the United States.

Methods:

The 2008 to 2012 Medical Expenditure Panel Survey data were used to identify colorectal (n = 540), female breast (n = 1568), and prostate (n = 1170) cancer survivors and individuals without a cancer history (n = 109 423). Excess economic burden attributable to cancer included per-person excess annual medical expenditures and productivity losses (employment disability, missed work days, and days stayed in bed). All analyses were stratified by cancer site and age (nonelderly: 18–64 years vs elderly: ≥65 years). Multivariable analyses controlled for age, sex, race/ethnicity, marital status, education, number of comorbidities, and geographic region. All statistical tests were two-sided.

Results:

Compared with individuals without a cancer history, cancer survivors experienced annual excess medical expenditures (for the nonelderly population, colorectal: $8647, 95% confidence interval [CI] = $4932 to $13 974, P < .001; breast: $5119, 95% CI = $3439 to $7158, P < .001; prostate: $3586, 95% CI = $1792 to $6076, P < .001; for the elderly population, colorectal: $4913, 95% CI = $2768 to $7470, P < .001; breast: $2288, 95% CI = $814 to $3995, P = .002; prostate: $3524, 95% CI = $1539 to $5909, P < .001). Nonelderly colorectal and breast cancer survivors experienced statistically significant annual excess employment disability (13.6%, P < .001, and 4.8%, P = .001) and productivity loss at work (7.2 days, P < .001, and 3.3 days, P = .002) and at home (4.5 days, P < .001, and 3.3 days, P = .003). In contrast, elderly survivors of all three cancer sites had comparable productivity losses as those without a cancer history.

Conclusions:

Colorectal, breast, and prostate cancer survivors experienced statistically significantly higher economic burden compared with individuals without a cancer history; however, excess economic burden varies by cancer site and age. Targeted efforts will be important in reducing the economic burden of colorectal, breast, and prostate cancer.

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Pelvic MRI findings in relapsed prostate cancer after radical prostatectomy

Abstract

Purpose/Objective

Little is known about the clinical impact of using multiparametric MRI to plan early salvage radiotherapy after radical prostatectomy. We aimed to evaluate the incidence and location of recurrence based on pelvic multiparametric MRI findings and to identify clinical variables predictive of positive imaging results.

Materials and methods

We defined radiological criteria of local and lymph node malignancy and reviewed records and MRI studies of 70 patients with PSA recurrence after radical prostatectomy. We performed univariate and multivariate analysis to identify any association between clinical, pathological and treatment-related variables and imaging results.

Results

Multiparametric MRI was positive in 33/70 patients. We found local and lymph node recurrence in 27 patients and 7 patients, respectively, with a median PSA value of 0.38 ng/ml. We found no statistically significant differences between patients with positive and negative multiparametric MRI for any variable. Shorter PSADT was associated with positive lymph nodes (median PSADT: 5.12 vs 12.70 months; p: 0.017).

Conclusions

Nearly half the patients had visible disease in multiparametric MRI despite low PSA. Positive lymph nodes incidence should be considered when planning salvage radiotherapy, particularly in patients with a short PSADT.

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Alcohol intake and invasive breast cancer risk by molecular subtype and race in the Carolina Breast Cancer Study

Abstract

Purpose

Alcohol is an established breast cancer risk factor, but there is little evidence on whether the association differs between African Americans and whites.

Methods

Invasive breast cancers (n = 1,795; 1,014 white, 781 African American) and age- and race-matched controls (n = 1,558; 844 white, 714 African American) from the Carolina Breast Cancer Study (Phases I–II) were used to estimate odds ratios (ORs) and 95 % confidence interval (CI) for pre-diagnosis drinks per week and breast cancer risk.

Results

African American controls reported lower alcohol intake than white controls across all age groups. Light drinking (0 to ≤2 per week) was more prevalent among African American controls. Moderate-to-heavy drinking was more prevalent in white controls. African Americans who reported drinking >7 drinks per week had an elevated risk compared to light drinkers [adjusted OR, 95% CI 1.62 (1.03–2.54)]. A weaker association was observed among whites [adjusted OR, 95% CI 1.20 (0.87–1.67)]. The association of >7 drinks per week with estrogen receptor-negative [adjusted OR, 95% CI 2.17 (1.25–3.75)] and triple-negative [adjusted OR, 95% CI 2.12 (1.12–4.04)] breast cancers was significant for African American, but not white women. We observed significantly elevated ORs for heavy intake at ages <25 and >50 years of age for African American women only. We found no evidence of statistical interaction between alcohol intake and oral contraceptive use or smoking.

Conclusions

Drinking more than seven alcoholic beverages per week increased invasive breast cancer risk among white and African American women, with significant increases only among African American women. Genetic or environmental factors that differ by race may mediate the alcohol–breast cancer risk association.

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Perinatal risk factors for acute myeloid leukemia

Abstract

Infectious etiologies have been hypothesized for acute leukemias because of their high incidence in early childhood, but have seldom been examined for acute myeloid leukemia (AML). We conducted the first large cohort study to examine perinatal factors including season of birth, a proxy for perinatal infectious exposures, and risk of AML in childhood through young adulthood. A national cohort of 3,569,333 persons without Down syndrome who were born in Sweden in 1973–2008 were followed up for AML incidence through 2010 (maximum age 38 years). There were 315 AML cases in 69.7 million person-years of follow-up. We found a sinusoidal pattern in AML risk by season of birth (P < 0.001), with peak risk among persons born in winter. Relative to persons born in summer (June–August), incidence rate ratios for AML were 1.72 (95 % CI 1.25–2.38; P = 0.001) for winter (December–February), 1.37 (95 % CI 0.99–1.90; P = 0.06) for spring (March–May), and 1.27 (95 % CI 0.90–1.80; P = 0.17) for fall (September–November). Other risk factors for AML included high fetal growth, high gestational age at birth, and low maternal education level. These findings did not vary by sex or age at diagnosis. Sex, birth order, parental age, and parental country of birth were not associated with AML. In this large cohort study, birth in winter was associated with increased risk of AML in childhood through young adulthood, possibly related to immunologic effects of early infectious exposures compared with summer birth. These findings warrant further investigation of the role of seasonally varying perinatal exposures in the etiology of AML.

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Inhibition of nuclear factor [kappa]B transcription activity drives a synergistic effect of cisplatin and oridonin on HepG2 human hepatocellular carcinoma cells.

Activation of nuclear factor [kappa]B (NF-[kappa]B) by cisplatin and other chemotherapeutics is responsible, at least in part, for the development of drug resistance in the treatment of hepatocellular carcinoma. Therefore, a combination of chemotherapeutics with NF-[kappa]B inhibitors could overcome resistance of cancer cells. Oridonin is a diterpenoid isolated from Rabdosia rubescens that can block the NF-[kappa]B signaling cascades. In this study, we investigated the synergistic effect of oridonin and cisplatin on human hepatocellular carcinoma HepG2 cells. Cell apoptosis and mitochondrial membrane potential loss were examined using Hoechst 33258 and rhodamine-123 staining, followed by flow cytometry, respectively. The expression of apoptosis-related proteins and NF-[kappa]B subunits was detected by real-time PCR and western blot. The activity of caspase 3 and 9 was measured using the Caspase Activity Kit. Electrophoretic mobility shift assay and the enzyme-linked immunosorbent assay-based kit were used to assess the DNA-binding activity of NF-[kappa]B. We found a synergistic antitumor effect between cisplatin and oridonin on HepG2 cells both in vitro and in vivo. In addition, the combination of cisplatin and oridonin synergistically induces apoptosis and regulates the expression and activity of several key apoptosis-related proteins. Furthermore, the combination treatment not only downregulates nuclear translocation of p50 and p65, but more significantly, decreases the transcription activity of all NF-[kappa]B subunits to a greater degree than either agent alone. Our results suggest that the synergistic effect between both agents is likely to be driven by the inhibition of transcription activity of NF-[kappa]B and the resulting increased apoptosis. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

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Self-reported Conflicts of Interest and Trial Sponsorship of Clinical Trials in Prostate Cancer Involving Radiotherapy.

Objectives: To examine the association between trial sponsorship and conflicts of interest (COI) with clinical trial conclusions for prostate cancer trials related to radiotherapy. Materials and Methods: The MEDLINE database was searched for all prostate cancer clinical trials published between 2004 and 2013 and identified 1396 studies. Two investigators independently identified trials published in the English language of >=30 patients, and extracted relevant data. Clinical trials were classified according to trial characteristics, sponsorship source and type, COI, and study conclusion, and analyzed by univariable and multivariable logistic regression. Results: Of 240 eligible trials, 160 (67.5%) evaluated drugs without radiotherapy, 60 (25%) involved radiotherapy, and 18 (7.5%) involved procedures without radiotherapy. Of the 60 radiotherapy trials eligible for analysis, positive sponsorship and potential COI were present in 58.3% and 20% of trials, respectively. Study conclusions were positive, negative, or neutral in 78.3%, 5%, and 16.7% of trials, respectively. No association was found between positive conclusions and either industry support of potential COI. Positive conclusions were reported in 86.7% and 83.3% of trials with sponsorship and COI, respectively, as compared with 75.6% and 77.1% of those without sponsorship (P=0.37) and COI (P=0.64). Sponsorship was significantly associated with radiotherapy trials combined with drugs (odds ratio 5.5, P=0.01) and higher-risk disease (odds ratio 4.71, P=0.01). Conclusions: The presence of sponsorship was associated with radiotherapy trials involving drugs or studying higher-risk prostate cancer. However, there were no identified associations between study conclusion and sponsorship type or COI. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

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The Benefit of Adjuvant Radiotherapy in High-grade Nonmetastatic Retroperitoneal Soft Tissue Sarcoma: A SEER Analysis.

Objectives: Controversy persists on the use of adjuvant radiotherapy (RT) in patients with retroperitoneal sarcoma (RPS). High-grade disease is known to be associated with decreased local control and overall survival (OS). Because RT has proven beneficial for local control and OS in patients with high-grade extremity soft tissue sarcoma, we evaluated the efficacy of adjuvant RT in high-grade RPS. Methods: The Surveillance, Epidemiology, and End Results database was used to identify patients with pathology-confirmed RPS from 1973 to 2010. Clinical characteristics and outcomes were analyzed. Results: Of 480 total patients, 144 (30.0%) received postoperative radiation. Patients who received adjuvant RT had improved median OS (36 mo) compared with those who did not (27 mo, hazard ratio [HR]=0.79, P=0.023). On multivariate analysis the use of adjuvant RT (HR=0.80; 95% confidence interval [CI], 0.65-0.98; P=0.029), male sex (HR=1.32; 95% CI, 1.10-1.59; P=0.003), age above 65 years (HR=1.38; 95% CI, 1.15-1.67; P=0.001), and increasing the Surveillance, Epidemiology, and End Results historical stage (HR=1.46; 95% CI, 1.21-1.76; P

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Biological Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Antibody Formation in Patients Treated With GM-CSF (Sargramostim) as Adjuvant Therapy of Melanoma.

Objectives: We investigated the development of binding and neutralizing antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients receiving prolonged therapy with GM-CSF as adjuvant therapy of melanoma and the impact of these antibodies on biological effects. Methods: Fifty-three patients with high-risk melanoma that had been surgically excised were treated with GM-CSF, 125 [mu]g/m2 daily for 14 days every 28 days for 1 year after surgical resection of disease. Serum samples for antibodies to GM-CSF were measured before treatment and on study days 155 and 351. Blood draws for testing biological effects were keyed to GM-CSF administration: days 0 (before), 15 (after 14 d on GM-CSF), 29 (after 14 d off GM-CSF), 155, and 351 (after 14 d on GM-CSF in the sixth and 13th cycle of treatment). Results: Of 53 patients enrolled, 43 were evaluable for the development of anti-GM-CSF antibodies. Of these, 93% developed binding antibodies and 42% developed both binding and neutralizing antibodies. The increase in the white blood cell count, percent eosinophils, or neopterin levels engendered by GM-CSF administration was abrogated or markedly decreased in patients with neutralizing antibodies but not in patients who developed only binding antibodies. Conclusions: Ninety-three percent of patients with melanoma treated with GM-CSF as adjuvant therapy develop antibodies to GM-CSF. In those with neutralizing antibodies, a diminution of the biological effects of GM-CSF was observed. The development of neutralizing antibodies might also abrogate the potential clinical benefit of this treatment and should be considered in the design of future clinical trials. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

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Correlation Between Standardized Uptake Value in Preneoadjuvant and Postneoadjuvant Chemoradiotherapy and Tumor Regression Grade in Patients With Locally Advanced Esophageal Cancer.

Purpose: To investigate whether positron emission tomography/computed tomography (PET/CT) initial and restaging imaging predicts for pathologic response measured by tumor regression grade (TRG) after preoperative chemoradiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: A retrospective review of 220 patients with stage II-III esophageal cancer treated with neoadjuvant CRT followed by surgery was performed. In total, 187 patients were eligible for statistical analysis. Pretreatment and posttreatment PET/CT scans were reviewed. Maximum standard uptake value (SUV) at the site of the primary tumor was recorded before and 6 weeks after neoadjuvant therapy. Upon completion of surgery, TRG was determined by a specialized site-specific gastrointestinal pathologist. Spearman correlation was used to compare pre, post, and change in maximum SUV, TRG, and overall survival. Results: The median follow-up was 24 months. Although no significant correlation was found between pretreatment SUV and TRG (r=0.073, P=0.32), post-CRT SUV, however, showed a significant positive correlation with TRG (r=0.374, P=70%. Conclusions: Changes in SUV uptake on PET/CT scans after CRT have prognostic value in predicting pathologic response of esophageal cancer after neoadjuvant therapy. Further studies are needed to validate the integration of PET/CT as a decision-making tool. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

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Perineural Invasion Predicts for Distant Metastasis in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiation and Surgery.

Objectives: The benefit of adjuvant chemotherapy in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) and surgery is controversial. We examined the association of perineural invasion (PNI) with outcomes to determine whether PNI could be used to risk-stratify patients. Materials and Methods: We performed a retrospective study of 110 patients treated with nCRT and surgery for LARC at our institution from 2004 to 2011. Eighty-seven patients were identified in our final analysis. We evaluated the association of PNI with locoregional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival, using log-rank and Cox proportional hazard modeling. Results: Fourteen patients (16%) were PNI+ and 73 patients (84%) were PNI-. The median follow-up was 27 months (range, 0.9 to 84 mo). The median DMFS was 13.5 months for PNI+ and median not reached (>40 mo) for PNI- (P

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Immunogenicity of Influenza Vaccination in Patients With Cancer.

Background: Influenza leads to significant morbidity and mortality in patients with cancer. Patients with cancer receiving chemotherapy may not mount an adequate immune response to the vaccine. We performed this pilot study to evaluate the immunogenicity of influenza vaccination in patients with cancer receiving chemotherapy. Materials and Methods: During the 2011 to 2012 influenza season, patients undergoing chemotherapy for solid tumors were given trivalent inactivated influenza vaccine either on the day of chemotherapy (schedule A) or a week before chemotherapy (schedule B) by a single 0.5 mL injection in the deltoid muscle region. This was not a randomized trial. Hemagglutination inhibition assays were performed on blood samples from these patients taken at baseline, and 4 weeks postvaccination. Seroconversion rate (>4-fold increase in titers) and seroprotection rates (postvaccination titers of >1:40) were calculated for each vaccine component: influenza A (H1N1), A (H3N2) and B. Results: A total of 18 patients received influenza vaccination as part of this pilot study. Of these, 8 patients received the vaccine on schedule A and 10 patients received the vaccine on schedule B. Geometric mean titers against each strain significantly improved after vaccination for both groups, as measured by signed rank test. Seroconversion to at least 1 strain was observed in 75% of patients on schedule A, and 70% of patients vaccinated on schedule B. Seroprotection to at least 1 strain was observed in 100% of patients in the schedule A group, and 60% of patients vaccinated on schedule B. Seroconversion and seroprotection rates against the 3 influenza strains were not significantly different between the 2 groups. Conclusions: Patients with nonhematological malignancies who are receiving chemotherapy mount an immune response to influenza vaccination. Timing of influenza vaccination in relation to chemotherapy does not seem to matter. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

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Factors Associated With Receipt of Radiation Therapy for Rectal Cancer.

Purpose: Appropriate treatment for cancer is vital to increasing the likelihood of survival; however, for rectal cancer, there are demonstrated disparities in receipt of treatment by race/ethnicity and socioeconomic status. We evaluated factors associated with receipt of appropriate radiation therapy for rectal cancer using data from the Florida Cancer Data System that had been previously enriched with detailed treatment information collected from a Centers for Disease Control and Prevention Comparative Effectiveness Research study. This treatment information is not routinely available in cancer registry data and represents a unique data resource. Materials and Methods: Using multivariable regression, we evaluated factors associated with receiving radiation therapy among rectal cancer cases stage II/III. Our sample (n=403) included cases diagnosed in Florida in 2011 who were 18 years and older. Cases clinically staged as 0/I/IV were excluded. Results: Older age (odds ratio=0.96; 95% confidence interval, 0.94-0.97), the presence of one or more comorbidities (0.61; 0.39-0.96), and receipt of surgical intervention (0.44; 0.22-0.90) were associated with lack of radiation. Conclusions: In this cohort of patients, sociodemographic factors such as race/ethnicity, insurance status, and socioeconomic status, did not influence the receipt of radiation. Further research is needed, however, to understand why aging, greater comorbidity, and having surgery present a barrier to radiation therapy, particularly given that it is a well-tolerated treatment in most patients. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

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HDAC5 controls the functions of Foxp3+ T-regulatory and CD8+ T cells

Abstract

Histone/protein deacetylases (HDACs) are frequently upregulated in human malignancies and have therefore become therapeutic targets in cancer therapy. However, inhibiting certain HDAC isoforms can have pro-tolerogenic effects on the immune system, which could make it easier for tumor cells to evade the host immune system. Therefore, a better understanding of how each HDAC isoform affects immune biology is needed to develop targeted cancer therapy. Here, we studied the immune phenotype of HDAC5^–/– mice on a C57BL/6 background. While HDAC5^–/– mice replicate at expected Mendelian ratios and do not develop overt autoimmune disease, their T-regulatory (Treg) cells show reduced suppressive function in vitro and in vivo. Likewise, CD4⁺ T-cells lacking HDAC5 convert poorly to Tregs under appropriately polarizing conditions. HDAC5^–/– Tregs show increased acetylation of Foxo1, which is deacetylated by HDAC5 and important for maintaining the Treg cell phenotype. To test if this attenuated Treg formation and suppressive function translated into improved anti-cancer immunity, we inoculated HDAC5^–/– mice and littermate controls with a lung adenocarcinoma cell line. Cumulatively, lack of HDAC5 did not lead to better anti-cancer immunity. We found that CD8⁺ T cells missing HDAC5 had a reduced ability to produce the cytokine, IFN-γ, in vitro and in vivo, which may offset the benefit of weakened Treg function and formation. Taken together, targeting HDAC5 weakens suppressive function and de-novo induction of Tregs, but also reduces the ability of CD8⁺ T cells to produce IFN-γ. This article is protected by copyright. All rights reserved.

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Clonidine, an alpha-2 adrenoceptor agonist relieves mechanical allodynia in oxaliplatin-induced neuropathic mice; potentiation by spinal p38 MAPK inhibition without motor dysfunction and hypotension

Abstract

Cancer chemotherapy with platinum-based antineoplastic agents including oxaliplatin frequently results in a debilitating and painful peripheral neuropathy. We evaluated the antinociceptive effects of the alpha-2 adrenoceptor agonist, clonidine on oxaliplatin-induced neuropathic pain. Specifically, we determined if (1) the intraperitoneal(i.p.) injection of clonidine reduces mechanical allodynia in mice with an oxaliplatin-induced neuropathy, and (2) concurrent inhibition of p38 mitogen-activated protein kinase(MAPK) activity by the p38 MAPK inhibitor SB203580 enhances clonidine's anti-allodynic effect. Clonidine(0.01-0.1mg kg⁻¹, i.p.), with or without SB203580(1-10nmol, intrathecal) was administered two weeks after oxaliplatin injection(10mg kg⁻¹, i.p.) to mice. Mechanical withdrawal threshold, motor coordination and blood pressure were measured. Post-mortem expression of p38 MAPK and ERK as well as their phosphorylated forms(p-p38 and p-ERK) were quantified 30 min or 4 hours after drug injection in the spinal cord dorsal horn of treated and control mice. Clonidine dose-dependently reduced oxaliplatin-induced mechanical allodynia and spinal p-p38 MAPK expression, but not p-ERK. At 0.1 mg kg⁻¹, clonidine also impaired motor coordination and decreased blood pressure. A 10 nmol dose of SB203580 alone significantly reduced mechanical allodynia and p-p38 MAPK expression, while a sub-effective dose(3nmol) potentiated the anti-allodynic effect of 0.03mg kg⁻¹ clonidine and reduced the increased p-p38 MAPK. Coadministration of SB203580 and 0.03mg kg⁻¹ clonidine decreased allodynia similar to that of 0.10mg kg⁻¹ clonidine, but without significant motor or vascular effects. These findings demonstrate that clonidine treatment reduces oxaliplatin-induced mechanical allodynia. The concurrent administration of SB203580 reduces the dosage requirements for clonidine, thereby alleviating allodynia without producing undesirable motor or cardiovascular effects. This article is protected by copyright. All rights reserved.

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Beyond a tumor suppressor: Soluble E-cadherin promotes the progression of cancer

Abstract

E-cadherin (E-cad) plays important roles in tumorigenesis as well as in tumor progression, invasion, and metastasis. This protein exists in two forms: a membrane-tethered form and a soluble form. Full-length E-cad is membrane tethered. As a type I transmembrane glycoprotein, E-cad mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. Soluble E-cad (sE-cad) is the extracellular fragment of the protein that is cleaved from the membrane after proteolysis of full-length E-cad. The production of sE-cad undermines adherens junctions, causing a reduction in cell aggregation capacity; furthermore, sE-cad can diffuse into the extracellular environment and the blood. As a paracrine/autocrine signaling molecule, sE-cad activates or inhibits multiple signaling pathways and participates in the progression of various types of cancer, such as breast cancer, ovarian cancer, and lung cancer, by promoting invasion and metastasis. This paper briefly reviews the role of sE-cad in tumorigenesis and tumor progression and its significance in clinical therapeutics. This article is protected by copyright. All rights reserved.

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Trajectory of body shape across the lifespan and cancer risk

Abstract

The influence of adiposity over life course on cancer risk remains poorly understood. We assessed trajectories of body shape from age 5 up to 60 using a group-based modeling approach among 73,581 women from the Nurses' Health Study and 32,632 men from the Health Professionals Follow-up Study. After a median of approximately 10 years of follow-up, we compared incidence of total and obesity-related cancers (cancers of the esophagus [adenocarcinoma only], colorectum, pancreas, breast [after menopause], endometrium, ovaries, prostate [advanced only], kidney, liver and gallbladder) between these trajectories. We identified 5 distinct trajectories of body shape: lean-stable, lean-moderate increase, lean-marked increase, medium-stable, and heavy-stable/increase. Compared with women in the lean-stable trajectory, those in the lean-marked increase and heavy-stable/increase trajectories had a higher cancer risk in the colorectum, esophagus, pancreas, kidney, and endometrium (relative risk [RR] ranged from 1.22 to 2.56). Early life adiposity was inversely while late life adiposity was positively associated with postmenopausal breast cancer risk. In men, increased body fatness at any life period was associated with a higher risk of esophageal adenocarcinoma and colorectal cancer (RR ranged from 1.23 to 3.01), and the heavy-stable/increase trajectory was associated with a higher risk of pancreatic cancer, but lower risk of advanced prostate cancer. The trajectory-cancer associations were generally stronger for non-smokers and women who did not use menopausal hormone therapy. In conclusion, trajectories of body shape throughout life were related to cancer risk with varied patterns by sex and organ, indicating a role for lifetime adiposity in carcinogenesis. This article is protected by copyright. All rights reserved.

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A meta-analysis of the association between Chlamydia pneumoniae infection and lung cancer risk

X Hua-Feng, W Yue-Ming, L Hong, D Junyi

Indian Journal of Cancer 2015 52(6):112-115

Objective: The association between Chlamydia pneumoniae infection and lung cancer risk was not clear with small number of cases in each study. The aim of this meta-analysis was to evaluate the correlation between pneumonia infection and lung cancer risk by pooling the open published papers. Materials and Methods: We searched the electronic databases of Medline, EMBASE, Web of Science, and China National Knowledge Infrastructure databases for publications related to the association between pneumonia infection and lung cancer risk. Odds ratio (OR) and its 95% confidence interval (95% CI) was used to assess the correlation. The data were pooled by Stata11.0 software (Stata Corporation, College Station, TX, USA). Results: Thirteen publications, involving 2549 lung cancer patients and 2764 controls were included in this meta-analysis. The pooled results indicated that the C. pneumoniae infection significant increased the risk of lung cancer OR = 2.07 (95% CI: 1.43–2.99) by random effect model. And for serum IgG, 12 publications reported the IgG positive rate in lung cancer patients and relative healthy controls. The pooled OR was 2.22 (95% CI: 1.41–3.50) by using the random effects model which indicated that the IgG positive rate was significantly higher in lung cancer patients than that of healthy controls. The sensitivity analysis indicated the pooled OR was not sensitive to a single study. However, Begger's funnel plot and Egger's line regression analysis indicated significant publications bias for this meta-analysis. Conclusions: According to the present published data, C. pneumoniae infection may increase the risk of lung cancer. However, for its significant publications and heterogeneity among the included studies, the conclusion should be interpreted cautiously.

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Transcatheter arterial infusion chemotherapy increases expression level of miR-142-5p in stage III colorectal cancer

D Shi, B Zhai, Y Zheng, R Ren, M Han, X Wang

Indian Journal of Cancer 2015 52(6):47-55

Objective: To investigate the expression level of miR-142-5p and its potential target gene endothelial PAS domain protein 1(EPAS1) in Stage III colorectal cancer during Transcatheter arterial infusion chemotherapy (TAI). Materials and Methods: Illumina high-throughput sequencing was used to obtain miRNA expression profiles of paired tumor and adjacent normal tissues from one patient received TAI 1 week before the operation and another patient directly underwent an operation. The expression levels of miR-142-5p was measured with both high-throughput sequencing and quantitative real time-polymerase chain reaction. Results: The expression levels of miR-142-5p, were significantly reduced in tumor tissues of stage III CRC, then significantly increased in tumor tissues receiving TAI and higher than tumor tissues without TAI. The apoptosis rate of HT-29 colon cancer cells was mildly increased after transfection with pre-miR-142. miR-142-5p could bind directly to the 3′untranslated region of endothelial PAS domain protein 1 and reduce its expression. Conclusions: miR-142-5p is a potential tumor suppressor in CRC and is upregulated in tumor tissues after TAI, suggesting its potential clinical values for testing the functionality of TAI and predicting the progress of CRC.

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Percutaneous computed tomography-guided iodine-125 seeds implantation for unresectable pancreatic cancer

B Liu, T Zhou, J Geng, F Zhang, J Wang, Y Li

Indian Journal of Cancer 2015 52(6):69-74

Background: To examine the safety and clinical efficacy of computed tomography (CT)-guided radioactive iodine-125 (125I) seeds implantation for patients with unresectable pancreatic cancer. Materials and Methods: A group of 26 patients with pathologically confirmed unresectable pancreatic cancer underwent percutaneous CT-guided 125I seeds implantation. Part of them received transarterial chemotherapy and/or percutaneous transhepatic cholangial drainage before or after seeds implantation. The primary endpoints were the objective response rates, local control rates, and overall survival. Results: CT scan 2 months after treatment revealed complete response (CR) in 8 patients, partial response (PR) in 9 patients. Overall response rate (CR + PR) is 65.38%. Local control rate was 88.46%. Median survival of the whole group was 15.3 months, whereas for Stage III and IV was 17.6 and 9.1 months, respectively. The estimated 1-year survival was 30.77%. Conclusions: We consider CT-guided 125I seeds implantation as a safe, effective, uncomplicated treatment for unresectable pancreatic cancer.

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Bronchopleural fistula after lung ablation: Experience in two cases and literature review

A Zheng, X Yang, X Ye, G Huang, Z Wei, J Wang, X Han, X Ni, M Meng

Indian Journal of Cancer 2015 52(6):41-46

Background: Bronchopleural fistula (BPF) complicating lung tumor ablation is rare but severe. The purpose of this article was to study its characteristics and treatments. Materials and Methods: Two of 682 (0.3%) sessions of lung microwave ablation (MWA) were complicated with BPF and documented. Two electronic databases were searched for reported cases of BPF after lung tumor ablation. Case selection and data collection were done by 3 independent reviewers. Results: A 56-year-old man and a 61-year-old woman developed BPF after MWA and died. Thirteen cases (mean age 63.8, 61.5% male) of BPF with adequate information were identified from 8 articles. Of the 13 cases, 5 (38.5%) had pulmonary co-morbidity, 3 (23.1%) had a history of pulmonary surgery, 7 (53.8%) had a target tumor adjacent or abutting pulmonary pleura, and 6 (46.2%) developed severe infections. After chest tube placement, pleurodesis, endoscopic therapy, surgery, and other treatments, 12 were cured and 1 died of BPF and pneumonia. Conclusion: BPF is a rare but severe complication of lung ablation, and the management needs a multidisciplinary and individualized treatment strategy.

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The role of video-assisted thoracoscopic surgery in management of the multiple ground-glass nodules

G Shao, W Ren, Z Feng, Z Peng

Indian Journal of Cancer 2015 52(6):75-79

Objective: We investigated the outcomes of patients with multiple ground-glass nodules (GGNs) to identify the role of video-assisted thoracoscopic surgery (VATS) in diagnosis and treatment. Patients and Methods: We included patients with multiple GGNs who were qualified for thoracoscopic surgery resection and analyzed the statistics. Results: Fifty-one GGNs were detected in 21 patients. There were 40 pure GGNs and 11 part-solid ones. Around 46 of the 51 lesions were resected via VATS. Four pure GGNs <10 mm and deep in the lung were proceeded with continuous follow-up. One pure GGN measuring 16 mm considered as subnodule and also deep in the lung underwent stereotactic ablative radiotherapy. Resection methods included lobectomy (1), segmentectomy (1), lobectomy + segmentectomy (6), lobectomy + wedge resection (10), and segmentectomy + wedge resection (3). Of the 46 resected lesions, 4 (8.7%) were atypical adenomatous hyperplasia (AAH), 23 (50%) were adenocarcinoma in situ(AIS), 15 (32.7%) were minimally invasive adenocarcinoma (MIA), 2 (4.3%) were invasive adenocarcinoma, one was pulmonary sclerosing hemangioma, and one was nonspecific fibrosis. Intersegmental lymph node metastasis was found in one of the 21 patients. No postoperational complication occurred in any of the patients. Conclusion: Multiple GGNs were generally independent primary lung cancers, mainly including AAH, AIS, MIA, rather than intrapulmonary metastasis. VATS was superior to thoracotomy for less invasive and shorter hospital stay.

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Ultrasonic guided percutaneous ethanol injection with or without combined radiofrequency ablation for hepatocellular carcinomas

L Kai, L Jia, W Zhi-Gang, Y Lei

Indian Journal of Cancer 2015 52(6):102-104

Objective: The aim of this retrospective study was to evaluate whether radiofrequency ablation (RFA) combined percutaneous ethanol injection (PEI) in the management of hepatocellular carcinoma (HCC) improves treatment outcomes. Patients and Methods: We retrospectively included 66 HCC patients who received RFA or RFA plus PEI from February 2011 to January 2014 in Jingmen No. 1 People's Hospital. Moreover, 31 cases received RFA plus PEI as the experiment group and 35 subjects treated with RFA aloe as the control group. The overall survival and treatment related complications were compared between the two groups. Results: For RFA group, the 1-year, 2-year, and 3-year survival rate were 82.0%, 69.3%, and 30.7%, respectively, with the median survival time of 27.1 months. For RFA plus PEI group, the 1-year, 2-year, and 3-year survival rate were 97.1%, 73.9%, and 37.5%, respectively, with the median survival time of 33.6 months. The overall survival of the two groups was not statistical different with the hazard ratio of 1.48 (P > 0.05); three cases of treatment associated complications were found in RFA group with 1 abscess, 1 pleural effusion, and 1 portal vein thrombosis. Moreover, 2 cases of complication were recorded in RFA plus PEI group with 1 pleural effusion and 1 portal vein thrombosis. The complicated incidence rate was not statistical different between the two groups (P < 0.05). Conclusion: The combination treatment of HCC was safe and had a slightly higher primary effectiveness rate than RFA alone.

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Artificial pneumothorax for pain relief during microwave ablation of subpleural lung tumors

X Yang, K Zhang, X Ye, A Zheng, G Huang, W Li, Z Wei, J Wang, X Han, X Ni, M Meng, Y Ni, Q Yuan, C Xing

Indian Journal of Cancer 2015 52(6):80-83

Background: When microwave ablation (MWA) is used for subpleural lesions, severe pain was the common side effect under the local anesthesia conditions during the procedure and postprocedure. To study the pain relief effect of artificial pneumothorax in the treatment of subpleural lung tumors with MWA. Materials and Methods: From February 2012 to October 2014, 37 patients with 40 subpleural lung tumors underwent MWA, including 17 patients of 19 sessions given artificial pneumothorax prior to MWA (group-I), and 20 patients of 21 sessions without artificial pneumothorax (group-II). Patient's pain assessment scores (10-point visual analog scale [VAS]) at during-procedure, 6, 12, 24, and 48 h after the MWA procedure and mean 24 h morphine dose were compared between the two groups. Complications of the artificial pneumothorax were also summarized. Results: Pain VAS were 0.53, 0.65, 1.00, 0.24, and 0.18 at during-procedure, 6, 12, 24, and 48 h for group-I and 5.53, 2.32, 2.82, 1.21, and 0.21 for group-II, respectively. Pain VAS in group I was significantly decreased at during-procedure, 6, 12, and 24 h after the MWA (P < 0.001). No statistical pain VAS difference was observed at 48 h after the MWA between the two groups (P > 0.05). The mean 24 h morphine dose was 5.00 mg in group-I and 12.63 mg in group-II (P = 0.000). "Artificial pneumothorax" related complications occurred in two patients from group-I, including one pleural effusion and one minor hemoptysis. No patient in group-I and group-II died during the procedure or in 30 days after MWA. Conclusion: Artificial pneumothorax is a safe and effective method for pain relief during MWA of subpleural lung tumors.

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Transradial arterial chemoembolization reduces complications and costs in patients with hepatocellular carcinoma

T Wu, R Sun, Y Huang, Z Wang, X Yin, Z Zhu, Z Zhao, J He

Indian Journal of Cancer 2015 52(6):107-111

Purpose: To improve patient comfort and reduce complications, clinical benefit of a transradial approach for transcatheter arterial chemoembolization (TACE) was evaluated in patients with hepatocellular carcinoma (HCC). Methods: A total of 284 patients with HCC for TACE was divided into transradial approach group (n = 126) and transfemoral approach group (n = 158). These two groups of cases were retrospectively compared with regard to complications, the procedural time, X-ray exposure time, length of hospitalization, and hospital costs. Results: There were lower incidence rates of complications including abdominal distension (42.85% vs. 87.97%, P> 0.001), vomiting (53.17% vs. 77.22%, P < 0.001), lumbago (1.59% vs. 97.46%, P < 0.001), and dysuria (0% vs. 62.03%, P < 0.001) in the transradial group as compared with the transfemoral group. The time required for catheterization and total X-ray exposure time were less in the transradial group compared with the transfemoral group (Pall < 0.001). The hospital stay time and costs required for catheterization were less in the transradial group compared with the transfemoral group (P < 0.001 and P = 0.001, respectively). In addition, hepatic angiography and TACE were completed in 100% and 99.2% cases in transfemoral and transradial groups, respectively. Conclusions: Transradial approach for TACE improves quality of life in patients with HCC by offering fewer complications and lower costs compared with transfemoral approach.

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Comparison of the gallbladder damage caused by microwave ablation and cryoablation in vivo porcine livers

Z Hao, C Wan, Q Han, S Ze, L Xin, F Weijun

Indian Journal of Cancer 2015 52(6):84-90

Purpose: To compare the imaging, anatomy, and histopathology of the porcine liver tissue adjacent to the gallbladder, as well as the temperature of the gallbladder wall and the damage degree of gallbladder wall at different times after microwave ablation (MWA) and cryoblation. Materials and Methods: Sixteen pigs were randomly divided into MWA group (Group M) and cryoblation group (Group C). The pigs were randomly divided into 8 subgroups according to their execution time, with 2 pigs in every subgroup. The pigs were executed immediately after operation, or at 1-, 2-, and 4-weeks postoperatively according to their assigned subgroup. The imaging and anatomy change of the liver ablation zone and the gallbladder wall were recorded. Histopathological observation was carried out for the damage portion of the gallbladder and the adjacent liver parenchyma. Results: (1) There were no significant statistical differences of the damage degree of the gallbladder between the two groups (P = 0.842). (2) Gallbladder wall edema occurred in Group M immediately after ablation (6/8), of which, 3 cases of gallbladder wall reached full-thickness damage; overlapping of ice ball and gallbladder wall occurred in Group C (5/8), of which, 4 cases of gallbladder wall reached full-thickness damage. However, there was neither perforation of gallbladder, biliary fistula, nor liver abscess in all cases. Conclusion: Both MWA and cryoablation for liver tissues adjacent to the gallbladder could lead to different damage degrees of the gallbladder wall, but not gallbladder perforation even under the condition of full-thickness damage.

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A meta-analysis of serum p16 gene promoter methylation for diagnosis of nonsmall cell lung cancer

R Yan, L Chi, X Zheng, R Sun, J You, X Ye

Indian Journal of Cancer 2015 52(6):116-118

Objectives: To evaluate the diagnostic value of serum p16 gene promoter methylation for diagnosis of nonsmall cell lung cancer (NSCLC). Materials and Methods: By searching the databases of PubMed and CNKI, we included all the published articles related serum p16 gene promoter methylation and nonsmall lung cancer. The true positive, false positive, false negative, and true negative data for each included publication were extracted by the reviewers. The diagnostic sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the receiver operating characteristic (ROC) were pooled by MetaDiSc1.4 software. Results: Finally, 13 manuscripts with 1440 subjects were involving in this diagnostic meta-analysis. The pooled sensitivity and specificity were 0.25 (95% confidence interval [CI]: 0.18–0.32) and 0.95 (95% CI: 0.93–0.97), respectively, with randomized effect model. The pooled positive likelihood ratio and negative likelihood ratio were 5.08 (95% CI: 3.00–8.62) and 0.69 (95% CI: 0.62–0.77) with fixed effect model and randomized effect model, respectively. The diagnostic ROC curve for the included 13 publications was pooled by statistical software MetaDiSc14.0 according to the Bayes theorem. The pooled area under the ROC was 0.72 with its standard error of 0.10. Conclusion: According to the published articles, high specificity and low sensitivity were found in this meta-analysis for the p16 gene promoter methylation in the diagnosis of NSCLC.

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Computed tomography-guided percutaneous microwave ablation treatment for lung metastases from nasopharyngeal carcinoma

H Qi, C Wan, X Li, L Zhang, Z Song, W Fan

Indian Journal of Cancer 2015 52(6):91-95

Background: The objective of this retrospective study was to evaluate the safety and efficacy of percutaneous microwave ablation (MWA) for treating lung metastases from nasopharyngeal carcinoma (NPC). Patients and Methods: From December 2012 to November 2014, 17 patients (15 males, and two females, averaged 45.7 years old) with lung metastases from NPC accepted computed tomography (CT)-guided percutaneous MWA. The average number of lung metastases was 1.7 (range: 1–4), and the biggest tumor diameter was 4.2 cm (range: 0.8–4.2 cm). Nineteen nodules located in the right lung and 10 nodules located in the left lung. A total of 29 ablation sites were performed to 29 lung metastases in 22 MWA sessions. Postoperative assessments of complete tumor necrosis rate, safety, local tumor progression, and survival period were carried out. Results: Of the 29 lesions, complete response was achieved for 27 lesions; residual tumor was found in one lesion 3 months postoperatively; and another lesion was found enlarged 3-month postoperatively with obvious enhancement. Four patients had a small amount of postoperative parenchyma bleeding and two patients had a small amount of pneumothorax. Six months after MWA treatment, new metastatic lesions appeared in six patients, five patients had new metastatic lesions inside the lung, and the other patient had metastatic lesions in the thoracic vertebra. The time for the appearance of new pulmonary metastases for the five patients was 4–20 months, averaged 7.2 months. Conclusion: CT-guided MWA is a promising treatment alternative for local tumor control in selected patients with lung metastases from NPC.

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MicroRNA-148a represents an independent prognostic marker in bladder cancer

Abstract

A previous study has demonstrated the roles of microRNA-148a (miR-148a) on apoptosis of bladder cancer cells. The goal of this study was to investigate whether the miR-148a expression level could serve as a new biomarker for the prognosis of bladder cancer patients. We collected a total of 126 bladder cancer samples. The expression level of miR-148a was determined with quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier method was used to analyze the overall survival. Cox regression analysis was further used to identify prognostic factors. The expression levels of miR-148a in bladder cancer tissues were identified (1.5 ± 0.3; P < 0.001). The bladder cancer patients in the low-expression group more frequently had a high tumor grade (P = 0.025), increased tumor recurrence (P = 0.002), and advanced lymph node (LN) metastasis (P = 0.001). Patient survival analysis revealed a clear positive correlation between miR-148a expression level and survival time of bladder cancer patients (P = 0.005, log-rank = 7.714). In univariate Cox proportional hazards regression analysis, we found that a low-expression level of miR-148a (P = 0.018), tumor grade (P = 0.006), lymph node metastasis (P = 0.001), and recurrence (P < 0.001) were associated with the prognosis of bladder cancer. In multivariate analysis, we found that miR-148a expression (RR = 0.206, 95 % CI 0.095–0.813, P = 0.029), tumor grade (RR = 0.714, 95 % CI 0.224–0.958, P = 0.714), lymph node metastasis (RR = 6.604, 95 % CI 3.192–12.547, P < 0.001), and recurrence (RR = 15.126, 95 % CI 6.714–22.025, P < 0.001) retained significance as an independent prognostic factor of bladder cancer survival (Table 3). All results have showed that miR-148a expression was decreased in bladder cancer specimens and reduced miR-148a expression was associated with poorer survival time, indicating that miR-148a may become a candidate factor for predicting the prognosis of bladder cancer.

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TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas

Abstract

Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.

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MicroRNA-520b affects the proliferation of human glioblastoma cells by directly targeting cyclin D1

Abstract

Glioblastoma (GBM) represents one of most common tumors in humans. However, the biological processes and molecular mechanisms of GBM are still unclear. It is known that microRNA-520b (miR-520b) participates in the development of various tumor progressions. The present study was to evaluate the level of miR-520b in GBM tissues and cells. We further investigated the molecular mechanisms of miR-520b in U87 and U251 cell lines. Here, our data showed that the expression levels of miR-520b were significantly reduced in clinical GBM tissues and cell lines. Accordingly, the expression levels of cyclin D1 were significantly increased in clinical GBM tissues and cell lines. Ectopic expression of miR-520b in U87 and U251 cells resulted in decreased cell proliferation and enhanced cell apoptosis. Further study characterized the 3′ untranslated region (3′-UTR) of cyclin D1 gene as a direct target of miR-520b in U87 and U251 cells as determined by luciferase reporter assays. In addition, ectopic expression of miR-520b led to the down-regulation of phosphorylated retinoblastoma (p-Rb, a downstream effector of cyclin D1), while the overexpression of cyclin D1 reversed the miR-520b-induced inhibition of p-Rb expression. In conclusion, this study highlights the importance of miR-520b in regulating the proliferation and apoptosis of GBM by directly targeting cyclin D1, and miR-520b may represent a potential therapeutic strategy for GBM.

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Unraveling Myelodysplastic Syndromes: Current Knowledge and Future Directions

Abstract

Myelodysplastic syndromes (MDS) affect more than 30,000 patients in the USA per year, most of whom are elderly, and these diseases are associated with dismal prognoses. The main features of MDS are ineffective hematopoiesis and aberrant myeloid differentiation. Furthermore, MDS are heterogeneous, both clinically and molecularly. This heterogeneity and the frequent occurrence of age-related comorbidities make the management of these diseases challenging. In fact, there have been no new drug approvals for MDS in the USA in the last 9 years, and few currently available investigational drugs are likely to be approved in the near future. Novel targeted treatment based on better understanding of the pathogenesis of MDS is needed to maximize patient outcomes. Here, we discuss new insights into diagnostic accuracy, prognostic assessment, pathogenic mechanisms, and effective treatments for MDS.

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Fast Helical Tomotherapy in a head and neck cancer planning study: is time priceless?

The last few years, in radiotherapy there has been a growing focus on speed of treatment delivery (largely driven by economical and commercial interests). This study investigates the influence of treatment tim...

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