TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells

Background: TWIST1 plays a key role in EMT-mediated tumor invasion and metastasis. Since bone metastasis is a hallmark of advanced prostate cancer and is detected in at least 85% of patients who die of this disease, it is of great importance to understand the regulation of the cellular signaling pathways involved in the metastatic process. Methods: Prostatic cell lines were analyzed using real time RT-PCR, chromatin immunoprecipitations (ChIP) and transfection of siRNA's and reporter constructs. Results: We report in this paper that TWIST1 is an androgen-regulated gene under tight regulation of NKX3-1. Androgens repress the expression of TWIST1 via NKX3-1, which is a prostate--specific tumor suppressor that is down-regulated in the majority of metastatic prostate tumors. We show that NKX3-1 binds to the TWIST1 promoter and that NKX3-1 over-expression reduces the activity of a TWIST1 promoter reporter construct, whereas NKX3-1 siRNA up-regulates endogenous TWIST1 mRNA in prostate cancer cells. Conclusion: Our finding that NKX3-1 represses TWIST1 expression emphasizes the functional importance of NKX3-1 in regulating TWIST1 expression during prostate cancer progression to metastatic disease.

via Cancer Cell International

Clinical and pathological features of hepatoid carcinoma of the ovary

Hepatoid carcinoma of the ovary (HCO), a rare invasive malignant tumor composed mainly of epithelioid cells, presented with unilateral or bilateral ovarian masses and elevated serum alpha-fetoprotein (AFP), has been found mainly in post-menopausal women. We hereby report on the case of a 53-year-old Chinese woman who presented with abdominal distension and a lower abdominal mass with high serum levels of CA-125 and AFP. She was later diagnosed with bilateral HCO. After surgery and following chemotherapy, the patient had no recurrence of tumor or ascites. The hepatoid cells were positive for AFP, p53 and CK7 by immunohistochemistry. Her serum CA-125 and AFP levels had decreased significantly after surgery. Our results suggest that testing and monitoring of serum levels of AFP and CA-125 are considered as potential biomarkers in the diagnosis and progression of this malignancy, and that tissue immunohistochemical staining for AFP, p53 and CK7, plays an important role in distinguishing HCO from other ovarian tumors.

via World Journal of Surgical Oncology

ALDH1 expression predicts outcome in node-negative rectal cancer

Expression of the cancer stem cell marker aldehyde dehydrogenase 1 is an independent predictor for poor prognosis in node-negative rectal cancer, researchers say.

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Fast access and early ligation of the renal pedicle significantly facilitates retroperitoneal laparoscopic radical nephrectomy procedures: modified laparoscopic radical nephrectomy

Background: The objective of this study was to develop a modified retroperitoneal laparoscopic nephrectomy and compare its results with the previous technique. Methods: One hundred retroperitoneal laparoscopic nephrectomies were performed from February 2007 to October 2011. The previous technique was performed in 60 cases (Group 1). The modified technique (n = 40) included fast access to the renal pedicle according to several anatomic landmarks and early ligation of renal vessels (Group 2). The mean operation time, mean blood loss, duration of hospital stay conversion rate and complication rate were compared between the groups. Results: No significant differences were detected regarding mean patient age, mean body mass index, and tumor size between the two groups (P >0.05). The mean operation time was 59.5 +/- 20.0 and 39.5 +/- 17.5 minutes, respectively, in Groups 1 and 2 (P <0.001). The mean intraoperative blood loss was 147 +/- 35 and 100 +/- 25 ml, respectively, in Groups 1 and 2 (P <0.001). No significant differences were detected regarding the conversion rate and the complication rate between the two groups (P >0.05). Conclusions: Early ligature using fast access to the renal vessels during retroperitoneal laparoscopic radical nephrectomy contributed to less operation time and intraoperative blood loss compared with the previous technique. In addition, the modified technique permits the procedure to be performed following the principles of open radical nephrectomy.

via World Journal of Surgical Oncology

Pelvic floor exercises after RP ‘sufficient’

Performing pelvic floor muscle training both before and after radical prostatectomy is no more effective at reducing postoperative urinary incontinence than performing the exercises after surgery, report researchers.

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Inflammation could hinder energy intake in advanced cancer

Energy intake, particularly energy density, is positively associated with energy balance in patients with advanced cancer, report Swedish researchers.

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Clinical reliability of radial forearm free flap in repair of buccal defects

Background: The ideal method for buccal defects should provide good outcome of both function and appearance; our goal is to highlight the reliability of radial forearm flap in buccal reconstruction. Methods: A retrospective study was conducted. From 2005 to 2012, 20 radial forearm flaps were used to repair the defects. We analyzed the superiority and reliability of the flap; in addition, we reviewed some related literature and made a comparison between radial forearm flap and platysma flap. Results: All radial forearm flaps totally survived, but two flaps suffered venous obstruction, hematoma, respectively. Radial forearm flap preserved the original interincisal distance well. In our follow-up, all patients had sufficient mouth-opening width (mean: 4.3 cm). Conclusion: Radial forearm flap is a reliable method for buccal defect reconstruction.

via World Journal of Surgical Oncology

Abnormal hematopoietic phenotypes in Pim kinase triple knockout mice: Pim kinase regulates hematopoiesis

Background: Pim (proviral insertion in murine lymphoma) kinases are a small family of constitutively active, highly conservative serine/threonine oncogenic kinases and have 3 members: Pim1, Pim2, and Pim3. Pim kinases are also implicated in the regulation of B- and T- cell responses to cytokines and hematopoietic growth factors. The roles of Pim kinases in the regulation of primitive hematopoietic stem cells (HSCs) are largely unknown. Methods: In the current study, Pim1-/-2-/-3-/- triple knockout (TKO) mice were used to determine the role of Pim kinases in hematopoiesis. Peripheral blood hematological parameters were measured in Pim TKO mice and age-matched wild-type (WT) controls. Primary, secondary, and competitive transplantations were performed to assay the long-term repopulating HSCs in Pim TKO mice. In vivo BrdU incorporation assay and ex vivo Ki67 staining and caspase 3 labeling were performed to evaluate the proliferation and apoptosis of HSCs in Pim TKO mice. Results: Compared to age-matched WT controls, Pim TKO mice had lower peripheral blood platelet count and exhibited erythrocyte hypochromic microcytosis. The bone marrow cells from Pim TKO mice demonstrated decreased hematopoietic progenitor colony-forming ability. Importantly, Pim TKO bone marrow cells had significantly impaired capacity in rescuing lethally irradiated mice and reconstituting hematopoiesis in primary, secondary and competitive transplant models. In vivo BrdU incorporation in long-term HSCs was reduced in Pim TKO mice. Finally, cultured HSCs from Pim TKO mice showed reduced proliferation evaluated by Ki67 staining and higher rate of apoptosis via caspase 3 activation. Conclusions: Pim kinases are not only essential in the hematopoietic lineage cell development, but also important in HSC expansion, self-renewal, and long-term repopulation.

via Journal of Hematology & Oncology

Expression of glioma-associated oncogene 2 (Gli 2) is correlated with poor prognosis in patients with hepatocellular carcinoma undergoing hepatectomy

Background: Our previous studies showed that glioma-associated oncogene (Gli)2 plays an important role in the proliferation and apoptosis resistance of hepatocellular carcinoma (HCC) cells. The aim of this study was to explore the clinical significance of Gli2 expression in HCC. Methods: Expression of Gli2 protein was detected in samples from 68 paired HCC samples, the corresponding paraneoplastic liver tissues, and 20 normal liver tissues using immunohistochemistry. Correlation of the immunohistochemistry results with clinicopathologic parameters, prognosis, and the expression of E-cadherin, N-cadherin, and vimentin were analyzed. Results: Immunohistochemical staining showed high levels of Gli2 protein expression in HCC, compared with paraneoplastic and normal liver tissues (P < 0.05). This high expression level of Gli2 was significantly associated with tumor differentiation, encapsulation, vascular invasion, early recurrence, and intra-hepatic metastasis (P < 0.05). There was a significantly negative correlation between Gli2 and E-cadherin expression (r = -0.302, P < 0.05) and a significantly positive correlation between expression of Gli2 and expression of vimentin (r = -0.468, P < 0.05) and N-cadherin (r = -0.505, P < 0.05). Kaplan-Meier analysis showed that patients with overexpressed Gli2 had significantly shorter overall survival and disease-free survival times (P < 0.05). Multivariate analysis suggested that the level of Gli2 expression was an independent prognostic factor for HCC. Conclusions: Expression of Gli2 is high in HCC tissue, and is associated with poor prognosis in patients with HCC after hepatectomy.

via World Journal of Surgical Oncology

Analysis of the clinical factors associated with anal function after intersphincteric resection for very low rectal cancer

Background: Intersphincteric resection (ISR) has been used to avoid permanent colostomy in very low rectal cancer patients. This study aimed to assess the surgical safety and oncologic and functional outcomes of ISR. Methods: The records of 30 consecutive very low rectal cancer patients who underwent ISR without neoadjuvant therapy were retrospectively analyzed; survival and locoregional recurrence rates were calculated by the Kaplan-Meier method. Incontinence was assessed by a functionality questionnaire and the Wexner score. Results: The median distance between the distal margin of the dentate line was 10 mm. A total of 12, 4, and 14 patients underwent partial ISR, subtotal ISR, and total ISR, respectively. The mean distal resection margin was negative in all cases, and circumferential resection margin was positive in two cases. Morbidity was 33.3%: anastomotic stricture in seven patients, colonic J-pouch prolapse in two patients, and an anovaginal fistula in one patient. During the median, 56.2-month follow-up period, local, distant, and combined recurrences occurred in four, three, and two patients, respectively. The 5-year overall and disease-free survival rates were 76.5% and 68.4%, respectively. Local recurrence rates were 5.2% for the patients with Tis-T2 tumors as compared with 45.5% for those with T3 tumors (P = 0.008). The mean Wexner scores and stool frequencies, 12 months after stoma closure in 19 patients, were 11.5 and 6.6 per 24 h, respectively. Significant differences were not seen in the Wexner scores between partial ISR and subtotal/total ISR (11.8 +/- 2.6 and 9.1 +/- 5.6). Stool frequency (P = 0.02), urgency (P = 0.04), and fragmentation (P = 0.015) were worse in patients with anastomotic stricture than in those without; there was no symptom improvement in patients with anastomotic stricture. Conclusions: The anastomotic strictures in patients undergoing ISR may have negatively affected anal function. For total ISR patients, at least, informed consent stating the possibility of a permanent colostomy is necessary.

via World Journal of Surgical Oncology

Primary choriocarcinoma of the colon: a case report and review of the literature

Choriocarcinoma usually arises in the uterus and gonads. Primary choriocarcinoma (PCC) in an extragenital organ is rare. When it occurs in the gastrointestinal tract, the stomach is the most common site. Only 12 cases of PCC of the colon have been reported in the world literature. Most cases were associated with adenocarcinoma. We report the case of a 36-year-old man with PCC of the colon and review the clinical characteristics of previously documented cases.

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European radiotherapy provision has ‘significant shortfalls’

A review published in The Lancet Oncology reveals significant shortfalls in radiotherapy equipment and manpower across Europe.

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Shorter surveillance intervals detect HCC earlier

Hepatocellular carcinoma surveillance in at-risk patients at intervals of less than 6 months picks up smaller tumors compared with longer intervals, show two recently published studies.

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Five genes hold key to meningioma make up

Research published in Science shows that mutations in five genes characterize most meningiomas.

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Cancer risk independent of folic acid supplementation

Folic acid supplementation does not increase or decrease the risk for cancer, suggests research published in The Lancet.

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Silencing of mutant p53 by siRNA induces cell cycle arrest and apoptosis in human bladder cancer cells

Background: p53 is the most frequently mutated tumor-suppressor gene in human cancers. It has been reported that mutations in p53 result not only in the loss of its ability as a tumor suppressor, but also in the gain of novel cancer-related functions that contribute to oncogenesis. The present study evaluated the potential of silencing of mutant p53 by small interfering RNA in the treatment of bladder cancer cells in vitro. Methods: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability and flow cytometry to detect cell cycle alterations and apoptosis. The related molecular mechanisms were assessed by western blotting. We also used the MTT assay and flow cytometry to investigate if silencing of mutant p53 by knockdown with small interfering (si)RNA would change the sensitivity to cisplatin treatment. Results: Using 5637 and T24 human bladder cancer cell lines characterized by mutations in p53, we found that silencing of the mutant p53 by RNA interference induced evident inhibition of cell proliferation and viability, which was related to the induction of G2 phase cell cycle arrest and apoptosis. Moreover, our study also showed that the p53-targeting siRNA cooperated with cisplatin in the inhibition of bladder cancer cells. Conclusions: These findings suggest that RNA interference targeting mutant p53 may be a promising therapeutic strategy for the treatment of bladder cancer.

via World Journal of Surgical Oncology

Prediagnostic androgen level not linked to prostate cancer outcome

Low prediagnostic levels of circulating sex hormones are not associated with more aggressive disease in patients with prostate cancer, say US researchers.

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Undifferentiated pleomorphic sarcoma with osteoclast-like giant cells of the female breast

The authors describe a case of undifferentiated pleomorphic sarcoma of the breast occurring in a 50-year-old woman who presented with a palpable mass in her right breast. She first noticed the mass one month previously. Core needle biopsy showed connective tissue including epithelioid and spindle cells. The patient underwent total mastectomy without axillary lymph node dissection. Based on examination of the excised tumor, the initial pathologic diagnosis was atypical spindle-shaped and ovoid cells with uncertain malignant potential. Histological findings with immunomarkers led to the final diagnosis of undifferentiated pleomorphic sarcoma.This case highlights a rare and interesting variant of primary breast sarcoma and the important role of immunohistochemistry in defining histological type and differential diagnosis. Hence, undifferentiated pleomorphic sarcoma has been a diagnosis of exclusion performed through sampling and critical use of ancillary diagnostic techniques.

via World Journal of Surgical Oncology

Prognostic analysis of early-stage squamous cell carcinoma of the vulva

Aim: The aim of this study was to analyze prognostic factors of early-stage squamous cell carcinoma of the vulva. Methods: A retrospective analysis was conducted on 35 patients who were treated for early-stage squamous cell carcinoma of the vulva at Sun Yat-sen University Cancer Center from January 1980 to December 2005. The Statistical Package for Social Science (SPSS) was used to compare the different strategies of operation and to analyze the prognostic factors. Results: Thirty-five patients had early-stage squamous cell carcinoma of the vulva. Of these cases, 26 were well differentiated, seven were moderately differentiated, and two were poorly differentiated. The five-year survival rate was 77.1%. Five cases were in FIGO stage 1a and 30 cases were in stage 1b; median survival times were 182.3 months and 152.5 months, and the five-year survival rates were 100% and 81.5% (P >0.05), respectively. The five-year survival of the patients who underwent local excision; radical vulvectomy and en bloc resection of inguinofemoral lymphadenectomy; orradical vulvectomyen bloc resection of inguinofemoral lymphadenectomy, and pelvic lymph nodes was 50%[ideographic comma]81.8%[ideographic comma]and 83.9%, respectively. For these cases, 74.3% of the tumors were medial while 25.7% were lateral, and the five-year survival rates of patients according to tumor location were 87.0% and 64.8% (P <0.05), respectively. The inguinal lymph node not increased and active were 16 cases (45.7%), and increased, active and hard were 17 cases (48.6%), and syncretic were two cases (5.7%), five-year survival rates were 73.3%, 92.9% and 50% (P <0.05), respectively. Of these cases, 74.3% of the tumors were cauliflower-like and 25.7% were nodular; five-year survival rates by tumor type were 91.3% and 66.7% (P <0.05), respectively. Conclusions: For patients with early-stage squamous cell carcinoma of the vulva, surgical operation is the primary, yet the best, treatment. The related prognostic factors were tumor location (lateral/medial), stage, gross morphology, and clinical state of the inguinal lymph node.

via World Journal of Surgical Oncology

Different mutations of the human c-mpl gene indicate distinct haematopoietic diseases

The human c-mpl gene (MPL) plays an important role in the development of megakaryocytes and platelets as well as the self-renewal of haematopoietic stem cells. However, numerous MPL mutations have been identified in haematopoietic diseases. These mutations alter the normal regulatory mechanisms and lead to autonomous activation or signalling deficiencies. In this review, we summarise 59 different MPL mutations and classify these mutations into four different groups according to the associated diseases and mutation rates. Using this classification, we clearly distinguish four diverse types of MPL mutations and obtain a deep understand of their clinical significance. This will prove to be useful for both disease diagnosis and the design of individual therapy regimens based on the type of MPL mutations.

via Journal of Hematology & Oncology

Smoking continues to threaten US public health

Research published in The New England Journal of Medicine shows that disease and mortality due to smoking have continually increased over the past 50 years in the USA.

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Periodontal health influences stem cell transplant success

Periodontal infection can increase the risk for developing bacteremia during the neutropenic phase of allogeneic hematopoietic stem cell transplantation, research suggests.

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Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors

Background: Oxaliplatin, an effective antineoplastic agent againstgastrointestinal tumors, can cause severe peripheral neurotoxicity, which seriously limits its clinical application. To date, there are no effective treatments for this complication. Ganglioside-monosialic acid (GM1) has been shown to protect neurons against injuries and degeneration. The aim of this study was to evaluate the effects of GM1 on preventing oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors. Methods: In this study, 120 patients with gastrointestinal tumors were enrolled, andthey received the treatment of XELOX (oxaliplatin and capecitabine) and FOLFOX4 (oxaliplatin, leukovolin and 5-fluorouracil). The patients were randomly divided into two groups, the experimental group and control group, with60 patients ineach. On the day chemotherapy was initiated, the experimental group received GM1 intravenously (100 mg once daily) for 3 days, while no neuroprotective agents were applied in the control group. The incidence rates and classification of neurotoxicity in the two groups were evaluated and the differences between the two groups were examined. Furthermore, whether GM1 affected the therapeutic effects of chemotherapy was also examined. Results: The grade of neurotoxicity in the experimental group was significantly lower than in the control group (P<0.05, Mann--Whitney U test). The probability of occurrence of low-grade neurotoxicity (grade 0 and 1) in the experimental group was higher than that in the control group (logistic ordinal regression); whereas the probability of occurrence of high-grade neurotoxicity (grade 2 and 3) in the experimental group was lower than in the control group (logistic ordinal regression). Conclusion: The data suggested that GM1 could reduce the grade of oxaliplatin-induced neurotoxicity and was an effective neuroprotective agent against oxaliplatin-induced high-grade neurotoxicity in patients with gastrointestinal tumors.

via World Journal of Surgical Oncology

Liposarcoma of the spermatic cord mimicking a left inguinal hernia: a case report and literature review

Liposarcoma of the spermatic cord (LSC) is a rare condition characterized by a painless inguinal or scrotal mass. To our knowledge, only about 200 cases have been previously reported in the literature. These tumors are often mistaken for common scrotal swellings, such as hydroceles and hernias. We present a LSC case in which a definitive diagnosis was obtained upon histological examination. We also provide a literature review of other cases that have been reported.

via World Journal of Surgical Oncology

Clear cell sarcoma of the jejunum: a case report

Background: Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a rare type of soft tissue sarcoma which exhibits morphological, immunohistochemical and ultrastructural similarity with malignant melanoma. It is rarely localized in the intestine and the natural history of this tumor is not yet clear.Case report: A 49-year-old woman presented with diffuse abdominal colicky pain and vomitus over the previous seven days. An X-ray of the abdomen revealed obstruction of the small intestine. The patient underwent contrast enhanced abdominal computerized tomography (CT), which confirmed the obstruction at the jejunum and an associated circumferential wall thickening extending about 3 cm in length, causing concentric narrowing of the lumen. At laparotomy, a mass was recognized at the level of the jejunum in the small intestine, which caused almost complete obstruction of the lumen. At the point of obstruction, adhered loops of small intestine were found. A segmental small bowel resection was performed with 5 cm clear margins and its respective mesenteric lymph nodes. Results: Histological examination of the specimen revealed a tumor (3 x 3 x 2 cm) with epithelioid cell characteristics and eosinophilic or clear cytoplasm and focal translucent nuclei. Immunohistochemistry was positive for S100, epithelial membrane antigen (EMA) and synaptophysin. The tumor was pankeratin AE1/AE2, GFAP, HMB45 and MART-1/Melan-A negative. Twelve lymph nodes were retrieved and were free of neoplastic infiltration. Cytogenetic examination revealed translocation of the EWSR1 gene. The patient had an uncomplicated postoperative course and left the hospital seven days after her admission in good general condition. After 20 months of follow-up the patient remains asymptomatic without any clinical or radiological evidence of recurrence. Conclusion: CCS sarcoma can be rarely localized in the jejunum. Due to its morphological similarity to malignant melanoma, cytogenetic examination is necessary for its diagnosis. Wide resection of the tumor and its respective lymph nodes was associated with a 20-month disease free survival in this patient.

via World Journal of Surgical Oncology

Increase of cyclooxygenase-2 inhibition with celecoxib combined with 5-FU enhances tumor cell apoptosis and antitumor efficacy in a subcutaneous implantation tumor model of human colon cancer

Background: The purpose of this study was to investigate the anti-tumor effect and explore the mechanisms of celecoxib (a selective cyclooxygenase-2 inhibitor) combined with 5-fluorouracil (5-FU) on the treatment of human colorectal cancer in a BALB/C nude mouse subcutaneous xenograft model. Methods: Effects of celecoxib combined with 5-FU on the proliferation of xenograft carcinoma induced by HT-29 were investigated. The apoptotic cells were detected by electron microscope and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. Immunohistochemistry and Western blot were used to estimate the expression of cytochrome C, caspase-3 and caspase-9. Results: Compared with the control group, treatment groups showed significant inhibition of tumor growth. More apoptotic cells existed after treatment with celecoxib combined with 5-FU. Cytochrome C, caspase-3 and caspase-9 were increased in treated groups, and more obviously in the drug combination group. Cyclooxygenase-2 (COX-2) were decreased after treatment with celecoxib only or combined with 5-FU. And the combined group showed a greater decrease. Conclusions: Celecoxib combined with 5-FU could inhibit the growth of tumors in vivo by inducing apoptosis and activation of the cytochrome C dependency apoptosis signal pathway. A decrease of COX-2 and an increase of cytochrome C[ideographic comma]caspase-3 and caspase-9 may be involved in this process.

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Effects of manual lymphatic drainage on breast cancer-related lymphedema: a systematic review and meta-analysis of randomized controlled trials

Background: Lymphedema is a common complication of axillary dissection for breast cancer. We investigated whether manual lymphatic drainage (MLD) could prevent or manage limb edema in women after breast-cancer surgery. Methods: We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) to evaluate the effectiveness of MLD in the prevention and treatment of breast-cancer-related lymphedema. The PubMed, EMBASE, CINAHL, Physiotherapy Evidence Database (PEDro), SCOPUS, and Cochrane Central Register of Controlled Trials electronic databases were searched for articles on MLD published before December 2012, with no language restrictions. The primary outcome for prevention was the incidence of postoperative lymphedema. The outcome for management of lymphedema was a reduction in edema volume. Results: In total, 10 RCTs with 566 patients were identified. Two studies evaluating the preventive outcome of MLD found no significant difference in the incidence of lymphedema between the MLD and standard treatment groups, with a risk ratio of 0.63 and a 95% confidence interval (CI) of 0.14 to 2.82. Seven studies assessed the reduction in arm volume, and found no significant difference between the MLD and standard treatment groups, with a weighted mean difference of 75.12 (95% CI, -9.34 to 159.58). Conclusions: The current evidence from RCTs does not support the use of MLD in preventing or treating lymphedema. However, clinical and statistical inconsistencies between the various studies confounded our evaluation of the effect of MLD on breast-cancer-related lymphedema.

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Symptomatic cardiac metastases of breast cancer 27 years after mastectomy: a case report with literature review - pathophysiology of molecular mechanisms and metastatic pathways, clinical aspects, diagnostic procedures and treatment modalities

Metastases to the heart and pericardium are rare but more common than primary cardiac tumours and are generally associated with a rather poor prognosis. Most cases are clinically silent and are undiagnosed in vivo until the autopsy. We present a female patient with a 27-year-old history of an operated primary breast cancer who was presented with dyspnoea, paroxysmal nocturnal dyspnoea and orthopnoea. The clinical signs and symptoms aroused suspicion of congestive heart failure. However, the cardiac metastases were detected during a routine cardiologic evaluation and confirmed with computed tomography imaging. Additionally, this paper outlines the pathophysiology of molecular and clinical mechanisms involved in the metastatic spreading, clinical presentation, diagnostic procedures and treatment of heart metastases. The present case demonstrates that a complete surgical resection and systemic chemotherapy may result in a favourable outcome for many years. However, a lifelong medical follow-up, with the purpose of a detection of metastases, is highly recommended. We strongly call the attention of clinicians to the fact that during the follow-up of all cancer patients, such heart failure may be a harbinger of the secondary heart involvement.

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Bioluminescence imaging of leukemia cell lines in vitro and in mouse xenografts: effects of monoclonal and polyclonal cell populations on intensity and kinetics of photon emission

Background: We investigated the utility of bioluminescence imaging (BLI) using firefly luciferase in monoclonal and polyclonal populations of leukemia cells in vitro and in vivo. Methods: Monoclonal and polyclonal human lymphoid and myeloid leukemia cell lines transduced with firefly luciferase were used for BLI. Results: Kinetics and dynamics of bioluminescence signal were cell line dependent. Luciferase expression decreased significantly over time in polyclonal leukemia cells in vitro. Transplantation of polyclonal luciferase-tagged cells in mice resulted in inconsistent signal intensity. After selection of monoclonal cell populations, luciferase activity was stable, equal kinetic and dynamic of bioluminescence intensity and strong correlation between cell number and light emission in vitro were observed. We obtained an equal development of leukemia burden detected by luciferase activity in NOD-scid-gamma mice after transplantation of monoclonal populations. Conclusion: The use of monoclonal leukemia cells selected for stable and equal luciferase activity is recommended for experiments in vitro and xenograft mouse models. The findings are highly significant for bioluminescence imaging focused on pre-clinical drug development.

via Journal of Hematology & Oncology

VRAM flap success for dorsal vaginal and perineal reconstruction

Reconstruction of the dorsal vagina or perineum using the vertical rectus abdominus myocutaneous flap following extensive surgery and intraoperative radiotherapy for rectal cancer results in favorable surgical and quality of life outcomes, research shows.

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HDL cholesterol key to fighting lymphoma

High-density lipoprotein cholesterol could provide a novel treatment target for patients with lymphoma, US scientists believe.

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Incomplete staging surgery as a major predictor of relapse of borderline ovarian tumor

Background: Borderline ovarian tumors (BOTs) are a subset of epithelial ovarian tumors with low malignant potential but significant risk of relapse (10% to 30%). Unfortunately, surgical prognostic factors for BOT relapse have not been clearly identified, probably due to the use of heterogeneous surgical definitions and limited follow-up. The aim of this study was to assess potential relapse risk factors using standard surgical definitions and long follow-up. Methods: All patients diagnosed with BOT for a period of more than 10 years in a single institution were included in the analysis. Complete surgical staging was defined as the set of procedures that follow standard guidelines for staging surgery (except lymphadenectomy), performed either with one or two interventions. Fertility-sparing surgeries that preserved one ovary and the uterus but included all the remaining procedures were classified as complete staging. The relationship between potential risk factors and time to BOT relapse was assessed by log-rank tests corrected for multiple comparisons and Cox regression. Results: Forty-six patients with a median follow-up of 5.4 years were included, of whom 91.3% had been diagnosed as FIGO stage I disease and 45.7% had received complete staging surgery. Five relapses were detected (10.9%), all of them in women who had been diagnosed with stage I disease and had received incomplete staging surgery. Log-rank tests confirmed the association between incomplete staging surgery and shorter time to BOT relapse. Conclusions: Complete staging surgery should be considered a cornerstone of BOT treatment in order to minimize the risk of relapse.

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Hospital-based home care can work for children with cancer

Hospital-based home care is a feasible alternative for children with cancer both regarding price and efficacy, show study findings.

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SLUG is activated by nuclear factor kappa B and confers human alveolar epithelial A549 cells resistance to tumor necrosis factor-alpha-induced apoptosis

Background: The role of tumor necrosis factor alpha (TNF-alpha) in cancer is complex with both apoptotic and anti-apoptotic roles proposed. However the mechanism is not clear. In the study, we designed to investigate the effect of TNF-alpha on the activation and expression of nuclear factor kappa B (NF-kappaB)/p65/SLUG/PUMA/Bcl-2 levels in human lung cancer A549 cell line, and in conditions of TNF-alpha-induced apoptosis. Methods: We have engineered three A549 cell lines that were transiently transfected with PUMA siRNA, SLUG siRNA and Bcl-2 siRNA, respectively. We have measured the in vitro effects of siRNA on apoptosis, and sensitivity to 20 ng/ml of TNF-alpha treatment for 24--48 h. Results: We found the NF-kappaB activity and PUMA mRNA/protein was significantly increased after treatment of TNF-alpha for 24 h in untreated A549 cells, and led to a significant increase in TNF-alpha-induced apoptosis, no significant increase of SLUG and Bcl-2 level was shown. However, after treatment of TNF-alpha for 48 h in untreated A549 cells, SLUG and Bcl-2 level was significant increased, and PUMA level was significant decreased, and TNF-alpha-induced apoptosis was significantly decreased compared to the apoptosis level after treatment of TNF-alpha for 24 h. Inhibition of the NF-kappaB activity could effectively decrease the PUMA level and increase the SLUG and Bcl-2 level. PUMA silencing by siRNA led to a significant decrease in TNF-alpha-induced apoptosis after treatment of TNF-alpha for 24 h. Bcl-2 and SLUG silencing by siRNA led to a significant increase in TNF-alpha-induced apoptosis for 48 h. Furthermore, SLUG silencing increased PUMA level and decreased Bcl-2 level. Conclusions: The findings suggested that TNF-alpha treatment promoted apoptosis via the NF-kappaB-dependent PUMA pathway. The anti-apoptotic role of TNF-alpha was via NF-kappaB-dependent SLUG and Bcl-2 pathway at a later time.

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DNA repair gene variants are associated with an increased risk of myelodysplastic syndromes in a Czech population

Background: Interactions between genetic variants and risk factors in myelodysplastic syndromes are poorly understood. In this case--control study, we analyzed 1 421 single nucleotide polymorphisms in 408 genes involved in cancer-related pathways in 198 patients and 292 controls. Methods: The Illumina SNP Cancer Panel was used for genotyping of samples. The chi-squared, p-values, odds ratios and upper and lower limits of the 95% confidence interval were calculated for all the SNPs that passed the quality control filtering. Results: Gene-based analysis showed nine candidate single nucleotide polymorphisms significantly associated with the disease susceptibility (q-value < 0.05). Four of these polymorphisms were located in oxidative damage/DNA repair genes (LIG1, RAD52, MSH3 and GPX3), which may play important roles in the pathobiology of myelodysplastic syndromes. Two of nine candidate polymorphisms were located in transmembrane transporters (ABCB1 and SLC4A2), contributing to individual variability in drug responses and patient prognoses. Moreover, the variations in the ROS1 and STK6 genes were associated with the overall survival of patients. Conclusions: Our association study identified genetic variants in Czech population that may serve as potential markers for myelodysplastic syndromes.

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Evaluation of chemosensitivity prediction using quantitative dose--response curve classification for highly advanced/relapsed gastric cancer

Background: The use of standard chemotherapy regimens has changed the application of chemosensitivity tests from all chemotherapy-eligible patients to those who have failed standard chemotherapy, which includes patients with highly advanced, relapsed, or chemoresistant tumors. Methods: We evaluated a total of 43 advanced primary and relapsed gastric cancers for chemosensitivity based on drug dose response curves to improve the objectivity and quality of quantitative measurements. The dose response curves were classified based on seven expected patterns. Instead of a binary chemosensitivity evaluation, we ranked drug sensitivity according to curve shapes and comparison with the peak plasma concentration (ppc) of each drug. Results: A total of 193 dose response curves were obtained. The overall informative rate was 67.4%, and 85.3% for cases that had a sufficient number of cells. Paclitaxel (PXL)and docetaxel tended to show a higher rank, while cisplatin (CIS) and 5-fluorouracil (5-FU) tended to show resistance, particularly among the 20 cases (46.5%) that had recurrent disease after receiving chemotherapy with CIS and S-1 (5-FU). As such, we speculate that the resistant pattern of the chemosensitivity test suggests that cells with acquired drug resistance were selected by chemotherapy. Indeed, we observed a change in the chemosensitivity pattern of a sample before and after chemotherapy in terms of PXL sensitivity, which was used after primary chemotherapy. Conclusions: These results suggest that: (i) the dose--response pattern provides objective information for predicting chemosensitivity; and (ii) chemotherapy may select resistant cancer cell populations as a result of the therapy.

via World Journal of Surgical Oncology

Askin's tumor: a case report and literature review

Askin's tumor is a primitive neuroectodermal tumor developing from the soft tissues of the chest wall. Its diagnosis approach is complex and requires a multidisciplinary team. Given the rarity of this entity, no regimen has been validated in the literature. We report two cases of Askin's tumor with a major response to polychemotherapy and surgical resection in one case. These cases show that treatment of Askin's tumor should be multimodal, requiring discussion in multidisciplinary tumor working groups.

via World Journal of Surgical Oncology

Bevacizumab QoL impact highlighted in ovarian cancer patients

The ICON7 study results suggest that improved progression-free survival with bevacizumab therapy for high-risk ovarian cancer may come at the cost of health-related quality of life.

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MRI ‘good accuracy’ for detecting residual breast cancer

Magnetic resonance imaging is superior to mammography for the detection of residual breast cancer after neoadjuvant chemotherapy, research confirms.

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Bladder cancer risk associated with childbearing factors

The risk for bladder cancer in women may decline with increased parity and older age at first birth, researchers report.

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Smartphone melanoma apps cause for concern

Smartphone applications that claim to be able to diagnose melanoma should be treated with extreme caution, say researchers.

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Benchmark study details rare spine pathology

A long-term analysis of a large intraspinal hemangiopericytoma patient cohort to date finds that survival and tumor recurrence is significantly associated with the pathologic grade of the cancer and not its location or degree of resection.

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Detection of reactive oxygen metabolites in malignant and adjacent normal tissues of patients with lung cancer

Background: Different types of reactive oxygen metabolites (ROMs) are known to be involved in carcinogenesis. Several studies have emphasized the formation of ROMs in ischemic tissues and in cases of inflammation. The increased amounts of ROMs in tumor tissues can either be because of their causative effects or because they are produced by the tumor itself. Our study aimed to investigate and compare the levels of ROMs in tumor tissue and adjacent lung parenchyma obtained from patients with lung cancer. Methods: Fifteen patients (all male, mean age 63.6 +/- 9 years) with non-small cell lung cancer were enrolled in the study. All patients were smokers. Of the patients with lung cancer, twelve had epidermoid carcinoma and three had adenocarcinoma. During anatomical resection of the lung, tumor tissue and macroscopically adjacent healthy lung parenchyma (control) that was 5 cm away from the tumor were obtained. The tissues were freshly frozen and stored at -20 [degree sign]C. The generation of ROMs was monitored using luminol- and lucigenin-enhanced chemiluminescence (CL) techniques. Results: Both luminol (specific for .OH, H2O2, and HOCl-) and lucigenin (selective for O2.-) CL measurements were significantly higher in tumor tissues than in control tissues (P <0.001). Luminol and lucigenin CL measurements were 1.93 +/- 0.71 and 2.5 +/- 0.84 times brighter, respectively, in tumor tissues than in the adjacent parenchyma (P = 0.07). Conclusion: In patients with lung cancer, all ROM levels were increased in tumor tissues when compared with the adjacent lung tissue. Because the increase in lucigenin concentration, which is due to tissue ischemia, is higher than the increase in luminol, which is directly related to the presence and severity of inflammation, ischemia may be more important than inflammation for tumor development in patients with lung cancer.

via World Journal of Surgical Oncology

Selenium and sulindac are synergistic to inhibit intestinal tumorigenesis in Apc/p21 mice

Background: Both selenium and non-steroidal anti-inflammatory drug (NSAID) sulindac are effective in cancer prevention, but their effects are affected by several factors including epigenetic alterations and gene expression. The current study was designed to determine the effects of the combination of selenium and sulindac on tumor inhibition and the underlying mechanisms. Results: We fed the intestinal tumor model Apc/p21 mice with selenium- and sulindac-supplemented diet for 24 weeks, and found that the combination of selenium and sulindac significantly inhibited intestinal tumorigenesis, in terms of reducing tumor incidence by 52% and tumor multiplicities by 80% (p<0.01). Mechanistic studies revealed that the combination of selenium and sulindac led to the significant induction of the expression of p27 and p53 and JNK1 phosphorylation, and led to the suppression of beta-catenin and its downstream targets. Impressively, the data also showed that demythelation on p21 promoter was associated with tumor inhibition by the combination of selenium and sulindac. Conclusions: The selenium is synergistic with sulindac to exert maximal effects on tumor inhibition. This finding provides an important chemopreventive strategy using combination of anti-cancer agents, which has a great impact on cancer prevention and has a promising translational potential.

via Journal of Hematology & Oncology

Palliative planning reduces out-of-hours hospital admissions

Being able to access an electronic palliative care summary for patients with cancer can help doctors make decisions during out-of-hours care and reduce the chances of unplanned hospital admissions, show UK study results.

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Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo

Background: Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated. Methods: The toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry. The contents of cyclin B1, Mcl-1, AIF, cytochrome C, insoluble and soluble tubulins were detected with western blotting. Microtubules were visualized with indirect immunofluorescence microscopy. The interaction between CDK1 and Mcl-1 was assessed with immunoprecipitation. Decreasing Mcl-1 and cyclin B1 expression were carried out through siRNA interference. The alterations of Mcl-1 and cyclin B1 in animal model were detected with either immunohistochemical staining or western blotting. In situ detection of apoptotic ratio was performed with TUNEL assay. Results: Our current results showed that selenite inhibited the growth of HL60 cells and induced mitochondrial-related apoptosis. Furthermore, we found that microtubule assembly in HL60 cells was altered, those cells were arrested at G2/M phase, and Cyclin B1 was up-regulated and interacted with CDK1, which led to down-regulation of the anti-apoptotic protein Mcl-1. Finally, in vivo experiments confirmed the in vitro microtubule disruption effect and alterations in Cyclin B1 and Mcl-1 levels by selenite. Conclusions: Taken together, the results from our study indicate that microtubules are novel targets of selenite in leukemic HL60 cells.

via Journal of Hematology & Oncology

Axillary web syndrome following secondary breast-conserving surgery: a case report

Background: Axillary web syndrome is a cause of significant morbidity in the early postoperative period after axillary surgery.Case presentationA patient developed axillary web syndrome after secondary breast surgery and recovered in 3 weeks through physical therapy and using Aescuven Forte.DiscussionThe pathogenesis of axillary web syndrome is not clear. It is reported that axillary surgery is the main cause. The presented case indicates that tissue injury might be an important cause of axillary web syndrome. Though axillary web syndrome is self-limiting, special physical therapy and Aescuven Forte can shorten the natural duration. Conclusion: Secondary breast surgery could cause axillary web syndrome. Physical therapy and Aescuven Forte could shorten the duration of the self-limited morbidity.

via World Journal of Surgical Oncology

Quarter of incident lung cancer slow growing or indolent

A quarter of incident lung cancers are slow growing or indolent, and may be overdiagnosed, suggest results from sequential low-dose computed tomography screening.

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Elderly rectal cancer patients at risk for stoma non-reversal

Half of elderly rectal cancer patients who undergo low anterior resection do not have stoma reversal surgery within 18 months, show US data.

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Ethnicity influences family involvement in end-of-life decisions

Research in Singapore reveals that, as cancer patients age, their families play a larger role in their healthcare decision-making, with patients themselves becoming less involved as their condition deteriorates.

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Diverse functions of miR-125 family in different cell contexts

MicroRNAs (miRNAs) are emerging as a novel class of non-coding RNA molecules that regulate gene expression at a post-transcriptional level. More than 1000 miRNAs have been identified in human cells to date, and they are reported to play important roles in normal cell homeostasis, cell metastasis and disease pathogensis and progression. MiR-125, which is a highly conserved miRNA throughout diverse species from nematode to humans, consists of three homologs hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125-2. Members of this family have been validated to be down-regulated, exhibiting its disease-suppressing properties in many different types of diseases, while they also have disease-promoting functions in certain contexts. MiR-125 targets a number of genes such as transcription factors, matrix-metalloprotease, members of Bcl-2 family and others, aberrance of which may lead to abnormal proliferation, metastasis and invasion of cells, even carcinomas. Furthermore, miR-125 plays a crucial role in immunological host defense, especially in response to bacterial or viral infections. In this review, we summarize the implication of miR-125 family in disease suppression and promotion, focusing on carcinoma and host immune responses. We also discussed the potential of this miRNA family as promising biomarkers and therapeutic targets for different diseases in future.

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TFPIalpha and TFPIbeta are expressed at the surface of breast cancer cells and inhibit TF-FVIIa activity

Background: Tissue factor (TF) pathway inhibitor-1 (TFPI) is expressed in several malignant tissues- and cell lines and we recently reported that it possesses anti-tumor effects in breast cancer cells, indicating a biological role of TFPI in cancer. The two main splice variants of TFPI; TFPIalpha and TFPIbeta, are both able to inhibit TF-factor VIIa (FVIIa) activity in normal cells, but only TFPIalpha circulates in plasma. The functional importance of TFPIbeta is therefore largely unknown, especially in cancer cells. We aimed to characterize the expression and function of TFPIalpha, TFPIbeta, and TF in a panel of tumor derived breast cancer cell lines in comparison to normal endothelial cells. Methods: TFPIalpha, TFPIbeta, and TF mRNA and protein measurements were conducted using qRT-PCR and ELISA, respectively. Cell-associated TFPI was detected after phosphatidylinositol-phospholipase C (PI-PLC) and heparin treatment by flow cytometry, immunofluorescence, and Western blotting. The potential anticoagulant activity of cell surface TFPI was determined in a factor Xa activity assay. Results: The expression of both isoforms of TFPI varied considerably among the breast cancer cell lines tested, from no expression in Sum149 cells to levels above or in the same range as normal endothelial cells in Sum102 and MDA-MB-231 cells. PI-PLC treatment released both TFPIalpha and TFPIbeta from the breast cancer cell membrane and increased TF activity on the cell surface, showing TF-FVIIa inhibitory activity of the glycosylphosphatidylinositol- (GPI-) anchored TFPI. Heparin treatment released TFPIalpha without decreasing the cell surface levels, thus indicating the presence of intracellular storage pools of TFPIalpha in the breast cancer cells. Conclusion: GPI-attached TFPI located at the surface of breast cancer cells inhibited TF activity and could possibly reduce TF signaling and breast cancer cell growth locally, indicating a therapeutic potential of the TFPIbeta isoform.

via Journal of Hematology & Oncology

MEK inhibition induced downregulation of MRP1 and MRP3 expression in experimental hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) exhibits strong intrinsic and acquired drug resistance which is the main obstacle to chemotherapy. Overexpression of ATP binding cassette (ABC) proteins correlates with activation of mitogen activated protein kinase (MAPK) pathway in HCC. Here, we systematically investigated the inhibition of MAPK pathway and its role in regulating HCC cell growth as well as ABC proteins MRP1 and MRP3 expression. Methods: The Raf1 kinase inhibitor (GW5074) and different MEK inhibitors (U0126 and AZD6244) were used to treat HCC cells to identify their effects on HCC cell growth and ABC proteins expression in vitro. Cell viability tests were performed after the treatment of MAPK pathway inhibitors and in combination with gemcitabine or doxorubicin. Western blot was applied to assess the changes of MAPK pathway and protein expression of MRP1 and MRP3. Flow cytometry was used to measure intracellular doxorubicin accumulation after the treatment of MEK inhibitors. Results: Both Raf1 inhibitor (GW5074) and MEK inhibitors (U0126 and AZD6244) suppressed HCC cell growth in a dose dependent manner. Pre-treatment of MEK inhibitor U0126 or AZD6244 sensitized HCC cells to gemcitabine or doxorubicin based chemotherapy. Raf1 inhibitor GW5074 had no effect on MRP1 and MRP3 protein expression. Treatment of gemcitabine or doxorubicin activated phosphorylated ERK and induced the upregulation of MRP1 and MRP3. MEK inhibitors U0126 and AZD6244 deactivated phosphorylated ERK, decreased endogenous MRP1 expression, reversed gemcitabine or doxorubicin induced MRP1 and MRP3 upregulation, and increased the intracellular doxorubicin accumulation. Conclusion: This study provides evidence that MEK inhibitors sensitize HCC cells to chemotherapy by increasing intracellular chemodrug accumulation. MEK inhibirors U0126 and AZD6244 reduced MRP1 as well as MRP3 expression, and may contribute partially to the sensitization. The combination of MEK inhibitor and conventional chemotherapy may offer new therapeutic option for the treatment of resistant HCC.

via Cancer Cell International

Hearing loss with radiotherapy for head and neck tumors

Radiotherapy for head and neck tumors has permanent, progressive, and dose-dependent effects on patients’ hearing, report researchers.

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Pure nongestational choriocarcinoma of the ovary: a case report

Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational choriocarcinoma of the ovary is extremely rare, and its diagnosis is very difficult during the reproductive years. We present a case of a 33-year-old woman diagnosed with pure nongestational ovarian choriocarcinoma. Following surgery, multiple courses of a chemotherapy regimen of etoposide, methotrexate, and actinomycin-D (EMA) were effective.

via World Journal of Surgical Oncology

Axillary treatment for patients with early breast cancer and lymph node metastasis: a systematic review

Background: For patients with early breast cancer and lymph node metastasis, axillary treatment is widely recommended. This is either surgical removal of the axillary lymph nodes, or axillary radiotherapy. The rationale for axillary treatment is that it will reduce the risk of recurrence in the axilla, and may improve survival. However, both treatments are associated with adverse effects, such as lymphedema, pain and sensory loss, and are costly to the health services and to patients. With improvements in adjuvant therapy, routine axillary treatment may no longer offer any overall advantage.Objectives: To assess the short and long term benefits and adverse effects of routine axillary treatment (axillary lymph node clearance or axillary radiotherapy) for patients with lymph node positive early-stage breast cancer. Methods: Criteria for potentially eligibility for the study will be that the participants are men and women with early breast cancer and lymph nodes with metastasis. The study compares either axillary treatment with no axillary treatment, or axillary node clearance with axillary radiotherapy, and the study is a randomized trial. Primary outcomes are axillary recurrence, disease-free and overall survival. Secondary outcomes include breast or chest wall recurrence, distant metastasis, time to axillary recurrence, axillary recurrence-free survival, arm morbidity, quality of life and health economic costs. The search strategy will include the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform (ICTRP) search portal. Two independent reviewers will assess studies for inclusion in the review, assess study quality and extract data. Characteristics of included studies will be described. Meta-analysis will be conducted using ReVman software.Comment: This review addresses an important clinical question, and results will inform clinical practice and health care policy.

via World Journal of Surgical Oncology

Beta blocker use linked to NSCLC patient survival

Beta blockers may boost survival in patients undergoing definitive radiotherapy for non-small-cell lung cancer, suggests research published in the Annals of Oncology.

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Aggressive surveillance questionable for eye melanoma recurrence

Patients treated for primary choroidal or ciliary body melanoma may not always benefit from an aggressive surveillance strategy for the detection of metastatic disease, caution US researchers.

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Targeted prostate biopsies skew proportion of high-risk cases

Image-targeted biopsy of the prostate leads to a substantial increase in the proportion of prostate cores identified as high risk compared with standard transrectal ultrasound-guided biopsy, the results of a UK study indicate.

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CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line

Background: Gastric cancer is a common and highly lethal malignancy in the world, but its pathogenesis remains elusive. In this study, we focus on the biological functions of CDK-associated Cullin1 (CAC1), a novel gene of the cullin family, in gastric cancer, which may help us to further understand the origin of this malignancy. Methods: The AGS and MGC803 gastric cancer cell lines and the GES-1 gastric mucosa cell line were selected for study. At first, CAC1 expressions of those cell lines were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blot examinations, then CAC1 small interfering RNA (CAC1-siRNA) were designed and transfected into the AGS cell line with a relatively high level of CAC1. Once CAC1 was silenced, a series of biological characteristics of AGS cells such as cell proliferation, cell cycle, apoptosis, and expressions of apoptosis-related genes (P53, BCL2 and BAX) were determined by MTT, flow cytometry, qRT-PCR and western blot, respectively. Results: CAC1 expression of AGS or MGC803 was much higher than that of GES-1. After CAC1 expression was effectively depressed by RNA interference in AGS cells, significant cell growth inhibition occurred. Furthermore, the proportion of cells treated with CAC1-siRNA increased in the G1 phase and decreased in the S phase, indicative of G1 cell cycle arrest. More importantly, the proportions of early/late apoptosis in AGS cells were enhanced with cis-diaminedichloroplatinum (cisplatin, CDDP) treatment, but to a higher extent with cisplatin plus CAC1-siRNA. Interestingly, BCL2 mRNA copies showed about a 30% decrease in the cisplatin group, but dropped by around 60% in the cisplatin plus CAC1-siRNA group. Conversely, the P53 mRNA expressions obtained nearly a two-fold increase in the cisplatin group, in addition to a five-fold increase in the cisplatin plus CAC1-siRNA group, and the BAX mRNA levels had almost a two- and four-fold augmentation, respectively. Meanwhile, P53, BAX and BCL2 showed the same alteration patterns in western blot examinations. Conclusions: CAC1 can promote cell proliferation in the AGS gastric cancer cell line. Moreover, it can prevent AGS cells from experiencing cisplatin-induced apoptosis via modulating expressions of P53, BCL2 and BAX.

via World Journal of Surgical Oncology

Intermittent therapy may be answer to treating drug-resistant melanoma

Findings from a study carried out in mice suggest that an intermittent dosing strategy may be the answer to combating lethal tumor resistance to the BRAF inhibitor vemurafenib, in patients with late-stage BRAF-mutated melanoma.

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Laparoscopy-assisted gastrectomy with D2 lymph node dissection for advanced gastric cancer without serosa invasion: a matched cohort study from South China

Background: Gastric cancer is a common malignancy worldwide and a common cause of death from cancer. Despite recent advances in multimodality treatment and targeted therapy, complete resection remains the only treatment that can lead to cure. This study was devised to investigate the technical feasibility, safety and oncologic efficacy of laparoscopy-assisted gastrectomy for advanced gastric cancer without serosa invasion. Methods: A retrospective matched cohort study was performed in south China comparing laparoscopy-assisted gastrectomy and open gastrectomy for advanced gastric cancer without serosa invasion. Eighty-three patients with advanced gastric cancer undergoing laparoscopy-assisted gastrectomy between January 2008 and December 2010 were enrolled. These patients were compared with 83 patients with advanced gastric cancer undergoing open gastrectomy during the same period. Results: There was no significant difference in clinicopathologic characteristics between the two groups. Regarding perioperative characteristics, the operation time and time to ground activities did not differ between the two groups, whereas the blood loss, transfused patient number, time to first flatus, time to resumption of diet, and postoperative hospital stay were significantly less in laparoscopy-assisted gastrectomy than in open gastrectomy (P <0.05). There was no statistically significant difference in postoperative morbidity and mortality. No significant difference in the number of lymph nodes dissected was observed between these two groups. There was no significant difference in the cumulative survival rate between the two groups. Conclusion: Laparoscopy-assisted gastrectomy with D2 lymphadenectomy is a safe and feasible procedure for advanced gastric cancer without serosa invasion. To be accepted as a choice treatment for advanced gastric cancer, well-designed randomized controlled trials comparing short-term and long-term outcomes between laparoscopy-assisted gastrectomy and open gastrectomy in a larger number of patients are necessary.

via World Journal of Surgical Oncology

Mirk/Dyrk1B mediates G0/G1 to S phase cell cycle progression and cell survival involving MAPK/ERK signaling in human cancer cells

Background: Mirk/Dyrk1B contributes to G0 arrest by destabilization of cyclin D1 and stabilization of p27kip1 to maintain the viability of quiescent human cancer cells, and it could be negatively regulated by mitogenic-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling. This study was performed to investigate the effect of Mirk/Dyrk1B on cell cycle and survival of human cancer cells involving MAPK/ERK signaling. Methods: The correlations between Mirk/Dyrk1B expression and active ERK1/2 detected by western blot in both ovarian cancer and non-small cell lung cancer (NSCLC) cells were analyzed by simple regression. Mirk/Dyrk1B unique phosphopeptides with sites associated with Mirk/Dyrk1B protein were isolated and quantitated by liquid chromatography coupled to tandem mass/mass spectrometry (LC-MS/MS) proteomics analysis. The human cancer cells were treated with small interfering RNAs (siRNAs) and/or U0126, an inhibitor of MEK for indicated duration, followed by investigating the alterations of cell cycle and apoptosis as well as related proteins examined by flow cytometry and Western blot, respectively. Results: Our study demonstrated the widely expressed Mirk/Dyrk1B proteins in the human cancer cells were positively correlated with the levels of activated ERK1/2. Moreover, Mirk/Dyrk1B protein expressions consistent with the tyrosine autophosphorylated levels in the human cancer cells were increased by U0126 or growth factor-depleted culture. Conversely, knockdown of Mirk/Dyrk1B by siRNA led to up-regulated activation of c-Raf-MEK-ERK1/2 pathway and subsequent changes in cell cycle proteins (cyclin D1, p27kip1), accompanied by increased growth rate and cells from G0/G1 into S of cell cycle which could be blocked by U0126 in a dose-dependent manner, indicating Mirk/Dyrk1B may sequester MAPK/ERK pathway, and vice versa. Whereas, combined Mirk siRNA and U0126 induced cell apoptosis in the human cancer cells. Conclusions: These data together show that Mirk/Dyrk1B mediates cell cycle and survival via interacting with MAPK/ERK signals and simultaneous inhibition of both pathways may be a novel therapeutic target for human cancer.

via Cancer Cell International

Cancer risk not increased in schizophrenia, bipolar disorder

Results from a large UK study suggest that people with severe mental illness are not at increased risk for developing common cancers.

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DNMT3A mutations and clinical features in Chinese patients with acute myeloid leukemia

Mutations in DNA methyltransferase 3A (DNMT3A) gene were recently demonstrated in acute myeloid leukemia(AML). Approximately 20% patients with AML carry DNMT3A gene mutations and was associated with a poor clinical outcome. but its clinical implications in Chinese AML patients are largely unknown .We analyzed 101 adult AML patients in china and found 14 patients (13.9%) harboring this mutation. 9 patient with M5, 2 patients with M1, 2patient with M2 and 1 patient with M3. We identified 11 missense mutation,2 nonsense and 30 bp deletion encompassing DNMT3A. The most common of them was predicted to affect 882Arg(in 4 patients).Double mutations were detected in two cases.10 of 33(43.5%). DNMT3A mutations occurred more frequently in older (age > 50y,p < 0.05) and the outcome is too badly for these patients. We concluded that DNMT3A mutations are highly recurrent in AML and is associated with distinct clinical and biologic characteristics and seems to be a useful as a prognostic marker.

via Cancer Cell International

‘PapGene’ test detects endometrial and ovarian cancers

Researchers have adapted the papanicolaou smear test currently used to detect cervical cancer so that it can be used to screen women for endometrial and ovarian cancers.

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Successful adjuvant bi-weekly gemcitabine chemotherapy for pancreatic cancer without impairing patients' quality of life

Background: Although adjuvant gemcitabine (GEM) chemotherapy for pancreatic cancer is standard, the quality of life (QOL) in those patients is still impaired by the standard regimen of GEM. Therefore, we studied whether mild dose-intensity adjuvant chemotherapy with bi-weekly GEM administration could provide a survival benefit with acceptable QOL to the patients with pancreatic cancer. Methods: After a phase I trial, an adjuvant bi-weekly 1,000 mg/m2 of GEM chemotherapy was performed in 58 patients with pancreatic cancer for at least 12 courses (Group A). In contrast, 36 patients who declined the adjuvant bi-weekly GEM chemotherapy underwent traditional adjuvant 5FU-based chemotherapy (Group B). Careful periodical follow-ups for side effects of GEM and disease recurrence, and assessment of patients' QOL using the EORTC QOL questionnaire (QLQ-C30) and pancreatic cancer-specific supplemental module (QLQ-PAN26) were performed. Retrospectively, the degree of side effects, patients' QOL, compliance rate, disease-free survival (DFS), and overall survival (OS) in Group A were compared with those in Group B. Results: No severe side effects (higher than Grade 2 according to the common toxicity criteria of ECOG) were observed, except for patients in Group B, who were switched to the standard GEM chemotherapy. Patients' QOL was better in Group A than B (fatigue: 48.9 +/- 32.1 versus 68.1 +/- 36.3, nausea and vomiting: 26.8 +/- 20.4 versus 53.7 +/- 32.6, diarrhea: 21.0 +/- 22.6 versus 53.9 +/- 38.5, difficulty gaining weight: 49.5 +/- 34.4 versus 67.7 +/- 40.5, P < 0.05). Compliance rates in Groups A and B were 93% and 47%. There was a significant difference in the median DFS between both groups (Group A : B =12.5 : 6.6 months, P < 0.001). The median OS of Group A was prolonged markedly compared with Group B (20.2 versus 11.9 months, P < 0.005). For OS between both groups, univariate analysis revealed no statistical difference in 69-year-old or under females, and T1--2 factors, moreover, multivariate analysis indicated three factors, such as bi-weekly adjuvant GEM chemotherapy, T2 or less, and R0. Conclusions: Adjuvant chemotherapy with bi-weekly GEM offered not only the advantage of survival benefits but the excellent compliance with acceptable QOL for postoperative pancreatic cancer patients.

via World Journal of Surgical Oncology

Oxaliplatin and bevacizumab disappoint for rectal cancer

The addition of bevacizumab and oxaliplatin to standard neoadjuvant chemoradiotherapy does not enhance clinical response rates in rectal cancer, show phase II study results.

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Resection of an intra-operative ruptured hepatocellular carcinoma with continuous pringle maneuver and in situ hypothermic perfusion through the inferior mesenteric vein - a case report

Intra-operative tumor rupture is a serious complication during resection of large hepatocellular carcinoma (HCC) leading to more blood loss. We report our experience in applying continuous Pringle maneuver with in situ hypothermic perfusion via inferior mesenteric vein catheterization to the portal vein of the remnant liver for resection during an extended left lobectomy of a large HCC which ruptured intraoperatively. Using this method, we successfully managed the patient without any further morbidity. This technique provides easier accessibility of in situ perfusion, decreases operative blood loss and prevents warm ischemic injury to the remnant liver during parenchymal transection. This method could be effective for the resection of large ruptured HCC.

via World Journal of Surgical Oncology

Penis shrinkage caution for prostate cancer patients

Men choosing prostate cancer treatment should be informed about the small risk for penis shrinkage, say US researchers who believe discussing the rare side effect could reduce the chance for patient regret.

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Intensity modulated radiotherapy for sinonasal malignancies with a focus on optic pathway preservation

Purpose: To assess if intensity-modulated radiotherapy (IMRT) can possibly lead to improved local control and lower incidence of vision impairment/blindness in comparison to non-IMRT techniques when treating sinonasal malignancies; what is the most optimal dose constraints for the optic pathway; and the impact of different IMRT strategies on optic pathway sparing in this setting.Methods and materials: A literature search in the PubMed databases was conducted in July, 2012. Results: Clinical studies on IMRT and 2D/3D (2 dimensional/3 dimensional) RT for sinonasal malignancies suggest improved local control and lower incidence of severe vision impairment with IMRT in comparison to non-IMRT techniques. As observed in the non-IMRT studies, blindness due to disease progression may occur despite a lack of severe toxicity possibly due to the difficulty of controlling locally very advanced disease with a dose <= 70 Gy. Concurrent chemotherapy's influence on the the risk of severe optic toxicity after radiotherapy is unclear. A maximum dose of <= 54 Gy with conventional fractionation to the optic pathway may decrease the risk of blindness. Increased magnitude of intensity modulation through increasing the number of segments, beams, and using a combination of coplanar and non-coplanar arrangements may help increase dose conformality and optic pathway sparing when IMRT is used. Conclusion: IMRT optimized with appropriate strategies may be the treatment of choice for the most optimal local control and optic pathway sparing when treating sinonasal malignancy.

via Journal of Hematology & Oncology

Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells

Background: Notch1 is a potent regulator known to play an oncogenic role in many malignancies including T-cell acute lymphoblastic leukemia (T-ALL). Tumor hypoxia and increased hypoxia-inducible factor-1alpha (HIF-1alpha) activity can act as major stimuli for tumor aggressiveness and progression. Although hypoxia-mediated activation of the Notch1 pathway plays an important role in tumor cell survival and invasiveness, the interaction between HIF-1alpha and Notch1 has not yet been identified in T-ALL. This study was designed to investigate whether hypoxia activates Notch1 signalling through HIF-1alpha stabilization and to determine the contribution of hypoxia and HIF-1alpha to proliferation, invasion and chemoresistance in T-ALL. Methods: T-ALL cell lines (Jurkat, Sup-T1) transfected with HIF-1alpha or Notch1 small interference RNA (siRNA) were incubated in normoxic or hypoxic conditions. Their potential for proliferation and invasion was measured by WST-8 and transwell assays. Flow cytometry was used to detect apoptosis and assess cell cycle regulation. Expression and regulation of components of the HIF-1alpha and Notch1 pathways and of genes related to proliferation, invasion and apoptosis were assessed by quantitative real-time PCR or Western blot. Results: Hypoxia potentiated Notch1 signalling via stabilization and activation of the transcription factor HIF-1alpha. Hypoxia/HIF-1alpha-activated Notch1 signalling altered expression of cell cycle regulatory proteins and accelerated cell proliferation. Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2) and MMP9, which increased invasiveness. Of greater clinical significance, knockdown of Notch1 prevented the protective effect of hypoxia/HIF-1alpha against dexamethasone-induced apoptosis. This sensitization correlated with losing the effect of hypoxia/HIF-1alpha on Bcl-2 and Bcl-xL expression. Conclusions: Notch1 signalling is required for hypoxia/HIF-1alpha-induced proliferation, invasion and chemoresistance in T-ALL. Pharmacological inhibitors of HIF-1alpha or Notch1 signalling may be attractive interventions for T-ALL treatment.

via Journal of Hematology & Oncology

Comparative efficacy of tandem autologous versus autologous followed by allogeneic hematopoietic cell transplantation in patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials

Background: Despite advances in understanding of clinical, genetic, and molecular aspects of multiple myeloma (MM) and availability of more effective therapies, MM remains incurable. The autologous-allogeneic (auto-allo) hematopoietic cell transplantation (HCT) strategy is based on combining cytoreduction from high-dose (chemo- or chemoradio)-therapy with adoptive immunotherapy. However, conflicting results have been reported when an auto-allo HCT approach is compared to tandem autologous (auto-auto) HCT. A previously published meta-analysis has been reported; however, it suffers from serious methodological flaws. Methods: A systematic search identified 152 publications, of which five studies (enrolling 1538 patients) met inclusion criteria. All studies eligible for inclusion utilized biologic randomization. Results: Assessing response rates by achievement of at least a very good partial response did not differ among the treatment arms [risk ratio (RR) (95% CI) = 0.97 (0.87-1.09), p = 0.66]; but complete remission was higher in the auto-allo HCT arm [RR = 1.65 (1.25-2.19), p = 0.0005]. Event-free survival did not differ between auto-allo HCT group versus auto-auto HCT group using per-protocol analysis [hazard ratio (HR) = 0.78 (0.58-1.05)), p = 0.11] or using intention-to-treat analysis [HR = 0.83 (0.60-1.15), p = 0.26]. Overall survival (OS) did not differ among these treatment arms whether analyzed on per-protocol [HR = 0.88 (0.33-2.35), p = 0.79], or by intention-to-treat [HR = 0.80 (0.48-1.32), p = 0.39] analysis. Non-relapse mortality (NRM) was significantly worse with auto-allo HCT [RR (95%CI) = 3.55 (2.17-5.80), p < 0.00001]. Conclusion: Despite higher complete remission rates, there is no improvement in OS with auto-allo HCT; but this approach results in higher NRM in patients with newly diagnosed MM. At present, totality of evidence suggests that an auto-allo HCT approach for patients with newly diagnosed myeloma should not be offered outside the setting of a clinical trial.

via Journal of Hematology & Oncology

A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer

Antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of action of therapeutic monoclonal antibodies (mAbs) such as cetuximab, rituximab and trastuzumab. Fc gamma receptors (FcgR) on human white blood cells are an integral part of the ADCC pathway. Differential response to therapeutic mAbs has been reported to correlate with specific polymorphisms in two of these genes: FCGR2A (H131R) and FCGR3A (V158F). These polymorphisms are associated with differential affinity of the receptors for mAbs. This review critically examines the current evidence for genotyping the corresponding single nucleotide polymorphisms (SNPs) to predict response to mAbs in patients with cancer.

via Journal of Hematology & Oncology

Vascular reconstruction raises pancreatic resection complication rates

Performing vascular reconstruction during surgical resection for pancreatic cancer is associated with a greater likelihood of postoperative adverse outcomes than resection alone, say US researchers.

via Med Wire News

Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in renal cell carcinoma

Background: Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis and are inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). {AU Query: Please verify that corrections made to previous sentence did not alter intended meaning.}In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1)-MMP, TIMP-1, and TIMP-2 in renal tissue samples of renal cell cancer and examined the correlation between their expression and clinicopathological parameters. Methods: Renal tissue samples from 76 patients with renal cell carcinoma were available for this study. To determine the expression of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues. Results: Mean MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the renal cell carcinomas was significantly higher than in the normal renal tissue (P <0.05). The RT-PCR data of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 did not show any significant correlation with tumor type or pathologic grade of renal cell carcinoma. MMP-2, MMP-9 and MT1-MMP mRNA expression increased significantly with the TNM stage of the tumor. Conclusions: Mean MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the renal cell carcinomas was significantly higher than in the normal renal tissue.

via World Journal of Surgical Oncology

Thromboprophylaxis does more harm than good in head and neck surgery

Patients undergoing oncologic head and neck surgery do not benefit from thromboprophylaxis, report researchers.

via Med Wire News