Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

A reliable and robust method for the upper thigh muscle quantification on computed tomography: toward a quantitative biomarker for sarcopenia

BACKGROUND: We aimed to evaluate the feasibility of the upper thigh level as a landmark to measure muscle area for sarcopenia assessment on computed tomography (CT). METHODS: In the 116 healthy subjects who performed CT scans covering from mid-abdomen to feet, the skeletal muscle area in the upper thigh level at the inferior tip of ischial tuberosity (SMA(UT)), the mid-thigh level (SMA(MT)), and L3 inferior endplate level (SMA(L3)) were measured by two independent readers. Pearson correlation coefficients between SMA(UT), SMA(MT), and SMA(L3) were calculated. Inter-reader agreement between the two readers were evaluated using intraclass correlation coefficient (ICC) and Bland-Altman plots with 95% limit of agreement (LOA). RESULTS: In readers 1 and 2, very high positive correlations were observed between SMA(UT) and SMA(MT) (r = 0.91 and 0.92, respectively) and between SMA(UT) and SMA(L3) (r = 0.90 and 0.91, respectively), while high positive correlation were observed between SMA(MT) and SMA(L3) (r = 0.87 and 0.87, respectively). Based on ICC values, the inter-reader agreement was the best in the SMA(UT) (0.999), followed by the SMA(L3) (0.990) and SMA(MT) (0.956). The 95% LOAs in the Bland-Altman plots indicated that the inter-reader agreement of the SMA(UT) (- 0.462 to 1.513) was the best, followed by the SMA(L3) (- 9.949 to 7.636) and SMA(MT) (- 12.105 to 14.605). CONCLUSION: Muscle area measurement at the upper thigh level correlates well with those with the mid-thigh and L3 inferior endpoint level and shows the highest inter-reader agreement. Thus, the upper thigh level might be an excellent landmark enabling SMA(UT) as a reliable and robust biomarker for muscle area measurement for sarcopenia assessment

Optimal radiation dose for patients with one to three lymph node positive breast cancer following breast-conserving surgery and anthracycline plus taxane-based chemotherapy: A retrospective multicenter analysis (KROG 1418)

BACKGROUND AND PURPOSE: This study was performed to determine optimal radiation dose in pN1 breast cancer patients who received breast conserving surgery (BCS) and anthracycline plus taxane (AT)-based chemotherapy. MATERIALS AND METHODS: Retrospective chart reviews were performed in 1,147 patients who were treated between January 2006 and December 2010. The impact of radiation dose on treatment outcomes was evaluated. RESULTS: Median follow-up time was 66 months. The 5-year rate of disease-free survival (DFS) was 93.2%. Larger tumor size (> 20 mm), positive lymphovascular invasion, high histologic grade, and high ratio of positive nodes (> 0.1) were significantly associated with inferior DFS. By using the 4 factors related to DFS, patients were categorized into high-risk (with >/= 3 factors) and low-risk (with 60.3 GyEQD2) was significantly associated with better DFS than the lower dose (</= 60.3 GyEQD2). However, the radiation dose did not impact DFS in the low-risk group. CONCLUSIONS: Dosing of radiation affects the outcome of post-BCS radiotherapy in pN1 breast cancer. Doses of over 60.3 GyEQD2 were associated with better outcome in the high-risk patients

Current routine practice and clinico-pathological characteristics associated with acute promyelocytic leukemia in Korea

Background: Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL. Methods: We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20‒80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012. Results: The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)×109/L and 2.7 to 124.0 (median 54.5)×109/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3‒44.1) s and 29 (24‒62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of ＞20 mg/mL. The D-dimer median value was 5,000 (686‒55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2‒19) d and 7 (2‒13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%). Conclusion: Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required

Anti-Osteoporotic Effects of Kukoamine B Isolated from Lycii Radicis Cortex Extract on Osteoblast and Osteoclast Cells and Ovariectomized Osteoporosis Model Mice

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. Previous study has demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing osteoblast differentiation. A bioactive compound, kukoamine B (KB), was identified from fractionation of an LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. In vivo experiments revealed that KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis

Quantitative analysis of tumor-specific BCL2 expression in DLBCL: refinement of prognostic relevance of BCL2

BCL2 overexpression has been reported to be associated with poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL). However, currently there is no consensus on the evaluation of BCL2 expression and only the proportion of BCL2 positive cells are evaluated for the determination of BCL2 positivity. This study aimed to define BCL2 positivity by quantitative analysis integrating both the intensity and proportion of BCL2 expression. BCL2 expression of 332 patients (221 patients for the training set and 111 patients for the validation set) with newly diagnosed DLBCL who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) were analyzed using the tumor-specific automated quantitative analysis (AQUA) scoring method based on multiplex immunofluorescence. In the training set, high BCL2 AQUA score (N = 86, 38.9%) was significantly associated with poor prognosis (p = 0.01, HR 2.00; 95% CI [1.15-3.49]) independent of international prognostic index, cell of origin, and MYC expression. The poor prognostic impact of the high BCL2 AQUA score was validated in the validation set. AQUA scoring of BCL2 expression incorporating both the intensity and proportion of BCL2 positive cells was independently associated with survival outcomes of patients with primary DLBCL treated with R-CHOP

CXCR6, a Newly Defined Biomarker of Tissue-Specific Stem Cell Asymmetric Self-Renewal, Identifies More Aggressive Human Melanoma Cancer Stem Cells

Background: A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. Conclusions/Significance: The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment

Hepatitis B and C virus prevalence in a rural area of South Korea: the role of acupuncture

A cross-sectional study evaluated the prevalence of and the risk factors for hepatitis C and B viruses among 700 adults above the age of 40 years in a rural area of South Korea. Seropositivity for hepatitis C virus antibody (11.0%, 95% confidence interval: 8.7–13.6) was higher than that for hepatitis B surface antigen (4.4%, 95% confidence interval: 3.0–6.2). Anti-hepatitis C virus seropositivity was associated with a history of repeated acupuncture (odds ratio=2.1, 95% confidence interval: 1.1–4.0), and blood transfusion (odds ratio=5.5, 95% confidence interval: 1.6–19.3) before 1992 when hepatitis C virus screening in blood donors became mandatory. Hepatitis C virus 2a was the most prevalent genotype, followed by 1b. Hepatitis C virus risk attributable to acupuncture was 38% (9% for men and 55% for women). Safer acupuncture practice has become a priority for hepatitis C virus prevention in South Korea