Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay

Background: The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents. Methods: In this study, the tumoursphere assay was validated in MCF-7 cells and used to screen novel marine algal compounds for potential anti-cancer stem cell (CSC) activity in vitro. Results: MCF-7 breast cancer cells were observed to generate tumourspheres or mammospheres after 3-5 days growth in anchorage-independent conditions and an apparent enrichment in potential CSCs was observed by an increase in the proportion of CD44high/CD24low marker-bearing cells and Oct4 expression compared to those in the bulk population grown in regular adherent conditions. Using this assay, a set of algal metabolites was screened for the ability to inhibit mammosphere development as a measure of potential anti-CSC activity. We report that the polyhalogenated monoterpene stereoisomers RU017 and RU018 isolated from the red alga Plocamium cornutum, both of which displayed no cytotoxicity against either adherent MCF-7 breast cancer or MCF-12A non-transformed breast epithelial cells, were able to prevent MCF-7 mammosphere formation in vitro. On the other hand, neither the brown algal carotenoid fucoxanthin nor the chemotherapeutic paclitaxel, both of which were toxic to adherent MCF-7 and MCF-12A cells, were able to inhibit mammosphere formation. In fact, pre-treatment with paclitaxel appeared to enhance mammosphere formation and development, a finding which is consistent with the reported resistance of CSCs to traditional chemotherapeutic agents. Conclusion: Due to the proposed clinical significance of CSC in terms of tumour initiation and metastasis, the identification of agents able to inhibit this subpopulation has clinical significance.

via Cancer Cell International

Independent of ErbB1 gene copy number, EGF stimulates migration but is not associated with cell proliferation in non-small cell lung cancer

Background: Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene. ErbB1 encodes epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, involved mainly in cell proliferation and survival. EGFR overexpression has been associated with more aggressive disease, poor prognosis, low survival rate and low response to therapy. ErbB1 amplification and mutation are associated with tumor development and are implicated in ineffective treatment. The aim of the present study was to investigate whether the ErbB1 copy number affects EGFR expression, cell proliferation or cell migration by comparing two different cell lines. Methods: The copies of ErbB1 gene was evaluated by FISH. Immunofluorescence and Western blotting were performed to determine location and expression of proteins mentioned in the present study. Proliferation was studied by flow cytometry and cell migration by wound healing assay and time lapse. Results: We investigated the activation and function of EGFR in the A549 and HK2 lung cancer cell lines, which contain 3 and 6 copies of ErbB1, respectively. The expression of EGFR was lower in the HK2 cell line. EGFR was activated after stimulation with EGF in both cell lines, but this activation did not promote differences in cellular proliferation when compared to control cells. Inhibiting EGFR with AG1478 did not modify cellular proliferation, confirming previous data. However, we observed morphological alterations, changes in microfilament organization and increased cell migration upon EGF stimulation. However, these effects did not seem to be consequence of an epithelial-mesenchymal transition. Conclusion: EGFR expression did not appear to be associated to the ErbB1 gene copy number, and neither of these aspects appeared to affect cell proliferation. However, EGFR activation by EGF resulted in cell migration stimulation in both cell lines.

via Cancer Cell International

New guidance on radioiodine therapy use after radiographic studies

Researchers have provided new evidence that could act as a guide for the use of radioiodine therapy after patients have undergone radiographic imaging studies that use iodine as a contrasting agent.

via Med Wire News

Changes in the MALT1-A20-NF-kappaB expression pattern may be related to T cell dysfunction in AML

To elucidate the characteristics of T-cell receptor (TCR) signal transduction in T-cells from acute myeloid leukemia (AML), the mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), A20, NF-kappaB and MALT1-V1 gene expression levels in CD3+ T cells sorted from the peripheral blood of patients with AML were analyzed by real-time PCR. A significantly lower MALT1 and A20 expression level was found in T cells from patients with AML compared with healthy controls (p = 0.045, p < 0.0001); however, the expression level of MALT1-V1 (variant 1) was significantly higher in the AML group than in the healthy control group (p = 0.006), and the expression level of NF-kappaB was increased in the AML group. In conclusion, the characteristics of the expression pattern of MALT1-A20-NF-kappaB and the distribution of MALT1 variants in T cells from AML were first characterized. Overall, low TCR-CD3 signaling is related to low MALT1 expression, which may related to T cell immunodeficiency, while the up-regulation of MALT1-V1 may play a role in overcoming the T cell activity by downregulating A20 in patients with AML, which may be related to a specific response to AML-associated antigens.

via Cancer Cell International

Azacitidine in patients with WHO-defined AML -- results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group

ObjectiveThe Austrian Azacitidine Registry is a multi-center database (ClinicalTrials.gov: NCT01595295). The nature and intent of the registry was to gain a comprehensive view of the use, safety and efficacy of the drug in a broad range of AML-patients treated in real-life scenarios.Patients and methods: The sole inclusion criteria were the diagnosis of WHO-AML and treatment with at least one dose of azacitidine. No formal exclusion criteria existed. A total of 155 AML-patients who were mostly unfit/ineligible for intensive chemotherapy, or had progressed despite conventional treatment, were included. True ITT-analyses and exploratory analyses regarding the potential prognostic value of baseline-variables/performance-/comorbidity-/risk-scores on OS, were performed. Results: In this cohort of 155 pretreated (60%), and/or comorbid (87%), elderly (45% >=75 years) AML-patients, azacitidine was well tolerated and efficacious, with an overall response rate (CR, mCR, PR, HI) of 45% in the total cohort (ITT) and 65% in patients evaluable according to IWG-criteria, respectively. Pre-treatment with conventional chemotherapy (P = .113), age <=/>80 years (P = .853), number of comorbidities (P = .476), and bone marrow (BM) blast count (P = .663) did not influence overall survival (OS). In multivariate analysis hematologic improvement alone (without the requirement of concomitant bone marrow blast reduction), although currently not regarded as a standard form of response assessment in AML, was sufficient to confer OS benefit (18.9 vs. 6.0 months; P = .0015). Further deepening of response after first response was associated with improved OS (24.7 vs. 13.7 months; P < .001). Conclusions: In this large cohort of AML-patients treated with azacitidine, age >80a, number of comorbidities and/or BM-blasts >30% did not adversely impact OS.

via Journal of Hematology & Oncology

New risk classification system proposed for prostate cancer

US researchers have put forward a risk stratification system for patients with intermediate-risk prostate cancer undergoing dose-escalated external-beam radiation therapy.

via Med Wire News

Development and characterization of a high-throughput in vitro cord formation model insensitive to VEGF inhibition

Background: Anti-VEGF therapy reduces tumor blood vessels, however, some vessels always remain. These VEGF insensitive vessels may help support continued tumor growth and metastases. Many in vitro assays examining multiple steps of the angiogenic process have been described, but the majority of these assays are sensitive to VEGF inhibition. There has been little focus on the development of high-throughput, in vitro assays to model the vessels that are insensitive to VEGF inhibition. Methods: Here, we describe a fixed end-point and kinetic, high-throughput stem cell co-culture model of cord formation. Results: In this system, cords develop within 24 hours, at which point they begin to lose sensitivity to VEGF inhibitors, bevacizumab, and ramucirumab. Consistent with the hypothesis that other angiogenic factors maintain VEGF-independent vessels, pharmacologic intervention with a broad spectrum anti-angiogenic antagonist (suramin), a vascular disrupting agent (combretastatin), or a combination of VEGF and Notch pathway inhibitors reduced the established networks. In addition, we used our in vitro approach to develop an in vivo co-implant vasculogenesis model that connects with the endogenous vasculature to form functional blood vessels. Similar to the in vitro system, over time these vessels become insensitive to VEGF inhibition. Conclusion: Together, these models may be used to identify novel drugs targeting tumor vessels that are not sensitive to VEGF inhibition.

via Journal of Hematology & Oncology

A pilot study: sequential gemcitabine/cisplatin and icotinib as induction therapy for stage IIB to IIIA non-small-cell lung adenocarcinoma

Background: A phase II clinical trial previously evaluated the sequential administration of erlotinib after chemotherapy for advanced non-small-cell lung cancer (NSCLC). This current pilot study assessed the feasibility of sequential induction therapy in patients with stage IIB to IIIA NSCLC adenocarcinoma. Methods: Patients received gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 75 mg/m2 on day 1, followed by oral icotinib (125 mg, three times a day) on days 15 to 28. A repeatcomputed tomography(CT) scan evaluated the response to the induction treatment after two 4-week cycles and eligible patients underwent surgical resection. The primary objective was to assess the objective response rate (ORR), while EGFR and KRAS mutations and mRNA and protein expression levels of ERCC1 and RRM1 were analyzed in tumor tissues and blood samples. Results: Eleven patients, most with stage IIIA disease, completed preoperative treatment. Five patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ORR=45%) and six patients underwent resection. Common toxicities included neutropenia, alanine transaminase (ALT) elevation, fatigue, dry skin, rash, nausea, alopecia and anorexia. No serious complications were recorded perioperatively. Three patients had exon 19 deletions and those with EGFR mutations were more likely to achieve a clinical response (P= 0.083). Furthermore, most cases who achieved a clinical response had low levels of ERCC1 expression and high levels of RRM1. Conclusions: Two cycles of sequentially administered gemcitabine/cisplatin with icotinib as an induction treatment is a feasible and efficacious approach for stage IIB to IIIA NSCLC adenocarcinoma, which provides evidence for the further investigation of these chemotherapeutic and molecularly targeted therapies.

via World Journal of Surgical Oncology

Tonsil resection prior to radiation improves survival

Performing tonsillectomy before radiotherapy in patients with stage I/II tonsil cancer is associated with improved survival, an analysis of US data indicates.

via Med Wire News

Skin cancer may increase subsequent primary malignancy risk

Research suggests that people with non-melanoma skin cancer are at moderately increased risk for developing other primary malignancies in the future, particularly breast and lung cancer and melanoma.

via Med Wire News

Epstein–Barr virus linked to improved gastric cancer survival

Research shows that Epstein–Barr virus positivity in gastric tumor cells is associated with improved prognosis.

via Med Wire News

Surgery extends life for metastatic colorectal cancer patients

Individuals with colorectal cancer that has metastasized to the liver or lung live longer after curative surgery plus chemotherapy than their counterparts who receive palliative chemotherapy alone, report researchers.

via Med Wire News

Recurrent cardiac myxoma in a 25 year old male: a DNA study

We present a 25 year old Caucasian male patient with multiple recurrences of cardiac myxomas after surgical removal of the original tumor. His mother was operated on for right ventriculare myxoma. The genetic analyses disclosed an aneuploid DNA content by flow cytometry analysis. The familial form of the cardiac myxomas must be distinguished from Carney complex syndrome. A long- term echocardiographic follow up is recommended to patients and their first degree relatives with cardiac myxomas.

via World Journal of Surgical Oncology

Cell sorting device improves detection of circulating tumor cells

An automated cell sorting device developed in the USA may allow circulating tumor cells to be detected with greater accuracy than by current methods, say researchers.

via Med Wire News

Protective effect of intraoperative nerve monitoring against recurrent laryngeal nerve injury during re-exploration of the thyroid

Background: Previous thyroid or parathyroid surgery induces scarring or distorts anatomy, and increases the risk of recurrent laryngeal nerve (RLN) injury for a reoperation. The benefit of intraoperative nerve monitoring (IONM) for re-exploration (a second nerve exploration) and reoperation has not been established. Methods: Two hundred and ten patients were given a thyroid or parathyroid reoperation at our hospital between 2001 and 2010. Using IONM, we re-explored 56 patients who had been operated on before June 2007. The injury rate in these patients was compared with that of the 15 patients re-explored without IONM between 2001 and 2006. Results: Of the 70 nerves that were re-explored using IONM, only one was incidentally injured, significantly fewer than the three injured in the 15 nerves re-explored without using IONM (1.43% vs. 20%, P = 0.0164). Conclusions: IONM helped prevent RLN damage when re-exploring nerves during thyroid and parathyroid surgery. We recommend the routine use of IONM in thyroid and parathyroid reoperations.

via World Journal of Surgical Oncology

S100A7 enhances invasion of human breast cancer MDA-MB-468 cells through activation of nuclear factor-kappaB signaling

Background: S100A7 signaling plays a critical role in the pathogenesis and progression of human breast cancers but the precise role and mechanism of S100A7 for tumor invasion remains unclear. in the present study, we investigated whether S100A7 overexpression could be mechanistically associated with the up-regulation of NF-kappaB, VEGF and MMP-9, resulting in the promotion of breast cancer cell invasion and growth, and vice versa. Methods: pcDNA3.1-S100A7 cDNA plasmid was constructed and transfected into the MDA-MB-468 cells. 4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect cell proliferation, Matrigel was used to detect cell mobility and invasion in vitro.The MMP-9 and VEGF expression and levels was detected by western blot and ELISA assay. NF-kappaB DNA binding activity was detected by Electrophoretic mobility shift assay. Results: Up-regulation of S100A7 by stable S100A7 cDNA transfection increased cell invasion and proliferation, whereas downregulation of S100A7 by small interfering RNA in S100A7 cDNA-transfected MDA-MB-468 cells decreased cell invasion and proliferation. Consistent with these results, we found that the up-regulation of S100A7 increased NF-kappaB DNA-binding activity and MMP-9 and VEGF expression. Down-regulation of S100A7 in S100A7 cDNA -transfected decreased NF-kappaB DNA-binding activity and MMP-9 and VEGF expression. Conclusions: Our data demonstrate that the S100A7 gene controls the proliferation and invasive potential of human MDA-MB-468 cells through regulation of NF-kappaB activity and its target genes, such as MMP-9 and VEGF expression. Down-regulation of S100A7 could be an effective approach for the down-regulation and inactivation of NF-kappaB and its target genes, such as MMP-9 and VEGF expression, resulting in the inhibition of invasion and growth.

via World Journal of Surgical Oncology

Tamoxifen breast changes predict survival

Women with breast cancer who experience a tamoxifen-related decrease in mammographic density have significantly better survival than patients whose breast density is unaffected by the agent, suggest study findings.

via Med Wire News

Radiotherapy improves QoL among elderly with bone metastases

Radiotherapy can significantly improve the quality of life of elderly individuals with cancer that has metastasized to the bone, show study results presented at the 2nd European Society for Radiotherapy and Oncology Forum in Geneva, Switzerland.

via Med Wire News

Tea and coffee may protect against oral cancer

Consumption of tea and coffee is inversely correlated with the risk for cancer of the oral cavity, a large population-based study suggests.

via Med Wire News

Multiphasic multidetector CT aids renal cell carcinoma differentiation

Multiphasic multidetector computed tomography may help clinicians discriminate clear cell renal cell carcinoma from oncocytoma, papillary RCC, and chromophobe RCC, study findings suggest.

via Med Wire News

HPV infection plays major role in oropharyngeal cancer

Infection with human papillomavirus type 16 has an important role in the etiology of oropharyngeal cancers, results from a large case–control study indicate.

via Med Wire News

Lower PSA linked to greater survival with sipuleucel-T in prostate cancer

Sipuleucel-T treatment may be of the most benefit to patients with metastatic castration-resistant prostate cancer who have low prostate specific antigen levels, say US researchers.

via Med Wire News

Smoking significant contributor to asbestos-related lung cancer

Quitting smoking significantly reduces a person’s chance of getting lung cancer after being exposed to asbestos, suggest study findings.

via Med Wire News

Cancer patients and physicians support assisted dying program

A Death with Dignity program, in which physicians can assist cancer patients with a prognosis of less than 6 months to end their lives, has been well-accepted by patients and their families, and received growing support from the physicians involved.

via Med Wire News

Dose-intense chemotherapy not superior for B-cell lymphoma

Compressing R-CHOP treatment cycles does not improve the outcome of elderly patients with diffuse large B-cell lymphoma, suggests research published in The Lancet Oncology.

via Med Wire News

Heart surgery risk in radiation-treated cancer survivors

Cancer survivors who are treated with chest radiation are nearly twice as likely to die in the years following major heart surgery as patients undergoing similar surgery who are never treated with radiation, a study shows.

via Med Wire News

Tamoxifen breast changes predict survival

Women with breast cancer who experience a tamoxifen-related decrease in mammographic density have significantly better survival than patients whose breast density is unaffected by the agent, suggest study findings.

via Med Wire News

Radiotherapy improves QoL among elderly with bone metastases

Radiotherapy can significantly improve the quality of life of elderly individuals with cancer that has metastasized to the bone, show study results presented at the 2nd European Society for Radiotherapy and Oncology Forum in Geneva, Switzerland.

via Med Wire News

C-reactive protein may be a prognostic factor in hepatocellular carcinoma with malignant portal vein invasion

Background: Hepatocellular carcinoma (HCC) has a high predilection for portal vein invasion, and the prognosis of HCC with malignant portal vein invasion is extremely poor. The objective of this study was to investigate the outcomes and the prognostic factor of recurrence in HCC patients with malignant portal vein invasion. Methods: We retrospectively reviewed the clinicopathologic data and outcomes of 83 HCC patients with malignant portal vein invasion and 1,056 patients without portal vein invasion who underwent liver resection. Results: Increased serum alkaline phosphatase (ALP) levels, increased maximum tumor size, and intrahepatic metastasis were predisposing factors for malignant portal vein invasion by multivariate analysis. The median disease-free survival and overall survival of HCC patients with malignant portal vein invasion was 4.5 months and 25 months, respectively. The 1-year, 2-year, and 3-year disease-free survival rates were 30.6%, 26.1%, and 21.2%, respectively, and the overall survival rates for HCC patients with malignant portal vein invasion were 68.6%, 54.2%, and 41.6%, respectively. The initial detection site was the lung in HCC patients with portal vein invasion and the liver in HCC patients without portal vein invasion. C-reactive protein (CRP) was a significant independent predictor of tumor recurrence in HCC with malignant portal vein invasion after surgery. Conclusions: Increased ALP levels, increased maximum tumor size, and intrahepatic metastasis were independent predictors of malignant portal vein invasion in HCC. CRP level was closely associated with the predisposing factor of tumor recurrence in HCC patients with malignant portal vein invasion after a surgical resection, and lung metastasis was common.

via World Journal of Surgical Oncology

Tea and coffee may protect against oral cancer

Consumption of tea and coffee is inversely correlated with the risk for cancer of the oral cavity, a large population-based study suggests.

via Med Wire News

Multiphasic multidetector CT aids renal cell carcinoma differentiation

Multiphasic multidetector computed tomography may help clinicians discriminate clear cell renal cell carcinoma from oncocytoma, papillary RCC, and chromophobe RCC, study findings suggest.

via Med Wire News

Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified

Background: Few studies have addressed the biological features of medullary breast carcinoma (MBC) in the context of clinical outcomes. We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between MBC and infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) using a large database. Methods: A total of 2,202 cases with pure IDC-NOS and 188 cases with typical MBC meeting the inclusion criteria were identified. The clinical and biological features, the overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups. Results: There were a higher proportion of patients diagnosed prior to 40 years of age in the MBC group compared to the IDC-NOS group. MBC cases demonstrated less aggressive tumor features such as lower tumor stage, smaller tumor size and a lower proportion of nodal involvement than IDC-NOS; however, immunohistochemical staining revealed that MBC displayed the triple-negative phenotype more often than IDC-NOS cases (40.4% versus 26.2%; P <0.001). Although the clinical behavior of MBC was not commensurate with its pathologic features, women diagnosed with MBC had a lower frequency of recurrence/metastasis (P = 0.032) and death (P = 0.042) than those with IDC-NOS, and the 10-year OS and RFS were significantly higher for MBC (91% and 74%) compared to IDC-NOS (81% and 64%). Moreover, multivariate analysis revealed that TNM stage was a statistically significant factor for survival. Conclusions: MBC in Chinese women demonstrated less aggressive behavior and better prognosis than IDC-NOS. This favorable outcome was maintained after 10 years.

via World Journal of Surgical Oncology

HPV infection plays major role in oropharyngeal cancer

Infection with human papillomavirus type 16 has an important role in the etiology of oropharyngeal cancers, results from a large case–control study indicate.

via Med Wire News

Surgical decompression improves recovery from neurological deficit and may provide a survival benefit in patients with diffuse large B-cell lymphoma-associated spinal cord compression: a case-series study

Background: Malignancy-associated spinal cord compression is generally treated by surgical decompression, radiotherapy or a combination of both. Since diffuse large B-cell lymphoma (DLBCL) is highly sensitive to both chemotherapy and radiotherapy, the role of surgical decompression in the treatment of DLBCL-associated spinal cord compression remains unclear. We therefore conducted a retrospective review to investigate the impact of surgical decompression on recovery from neurological deficit caused by DLBCL-associated spinal cord compression and patients' overall survival. Methods: Between March 2001 and September 2011, 497 newly diagnosed DLBCL patients were reviewed, and 11 cases had DLBCL-associated spinal cord compression. Six cases were treated surgically and five cases nonsurgically. Results: The rates of complete recovery from neurological deficit were 100% (6/6) and 20% (1/5) for patients in the surgical and nonsurgical groups, respectively (P = 0.015), while the median survival for patients in the surgical and nonsurgical groups was 48.6 months and 17.8 months, respectively (P = 0.177). Conclusions: We conclude that surgical decompression can improve recovery from neurological deficit in patients with DLBCL-associated spinal cord compression, possibly providing these patients a survival benefit.

via World Journal of Surgical Oncology

Osteosarcoma of the spine: surgical treatment and outcomes

Background: The goal of this study was to determine whether there are correlations between various options of surgical treatment and long-term outcome for spinal osteosarcoma. Methods: This was a retrospective review of 16 patients with spinal osteosarcoma, who underwent surgical treatment from 1999 to 2010. Seven patients were given total en bloc spondylectomy (TES), while nine received piecemeal resection (there were seven cases of total piecemeal spondylectomy, one of sagittal resection, and one of vertebrectomy). The outcome and prognosis of the patients were evaluated, grouped by surgical treatment. Results: All 16 cases were followed for an average of 42.4 months. At follow-up, all patients noted that pain had eased or had gradually disappeared. Three months after surgery, eight patients (50.0%) had improved 1 to 2 grades in their neurological status, based on Frankel scoring. Six (37.5%) patients experienced local recurrence of the tumor, nine (56.3%) had metastases, and five (31.3%) died of the disease. Of the six patients who received a wide or marginal en bloc resection, none developed local recurrence or died from the disease. Conversely, of the ten patients who received intralesional or contaminated resections, six (60%) relapsed and five (50%) died from the disease. Conclusions: TES, with a wide margin, should be planned for patients with osteosarcoma of the cervical and thoracolumbar spine, whenever possible. When the patients are not candidates for en bloc resection, total piecemeal spondylectomy is an appropriate choice for osteosarcoma in the mobile spine.

via World Journal of Surgical Oncology

Clinicopathological patterns and challenges of management of colorectal cancer in a resource-limited setting: a Tanzanian experience

Background: Colorectal cancer is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries, probably due to the acquisition of a western lifestyle. However, information regarding colorectal cancer in Tanzania and the study area in particular is limited. This study was conducted in our local setting to describe the clinicopathological pattern of colorectal cancer and highlight the challenging problem in the management of this disease. Methods: This was a retrospective study of histologically confirmed cases of colorectal cancer seen at Bugando Medical Center between July 2006 and June 2011. Data were retrieved from patients' files and analyzed using SPSS computer software version 17.0. Results: A total of 332 colorectal cancer patients were enrolled in the study, representing 4.7% of all malignancies. Males outnumbered females by a ratio of 1.6:1. The median age of patients at presentation was 46 years. The majority of patients (96.7%) presented late with advanced stages. Lymph node and distant metastasis at the time of diagnosis was recorded in 30.4% and 24.7% of cases, respectively. The rectosigmoid region was the most frequent anatomical site (54.8%) involved and adenocarcinoma (98.8%) was the most common histopathological type. The majority of adenocarcinomas (56.4%) were moderately differentiated. Mucinous and signet ring carcinomas accounted for 38 (11.6%)and 15 (4.6%) patients, respectively. Three hundred and twenty-six (98.2%) patients underwent surgical procedures for colorectal cancer. Only 54 out of 321 (16.8%) patients received adjuvant treatment. Postoperative complication and mortality rates were 26.2% and 10.5%, respectively. The overall median duration of hospital stay was 12 days. Only nine out of 297 survivors (3.0%) were available for follow-up at the end of 5 years. Cancer recurrence was reported in 56 of 297 survivors (18.9%). Data on long-term survival were not available as the majority of patients were lost to follow-up. Conclusions: Colorectal cancer is not uncommon in our environment and shows a trend towards a relative young age at diagnosis and the majority of patients present late with advanced stage. There is a need for screening of high-risk populations, early diagnosis and effective cost-effective treatment and follow-up to improve outcome of these patients.

via World Journal of Surgical Oncology

Smoking significant contributor to asbestos-related lung cancer

Quitting smoking significantly reduces a person’s chance of getting lung cancer after being exposed to asbestos, suggest study findings.

via Med Wire News

Cancer patients and physicians support assisted dying program

A Death with Dignity program, in which physicians can assist cancer patients with a prognosis of less than 6 months to end their lives, has been well-accepted by patients and their families, and received growing support from the physicians involved.

via Med Wire News

Lower PSA linked to greater survival with sipuleucel-T in prostate cancer

Sipuleucel-T treatment may be of the most benefit to patients with metastatic castration-resistant prostate cancer who have low prostate specific antigen levels, say US researchers.

via Med Wire News

MicroRNA-495 inhibits proliferation of glioblastoma multiforme cells by downregulating cyclin-dependent kinase 6

Background: Glioblastoma multiforme (GBM) is the most aggressive type of glioma and carries the poorest chances of survival. There is therefore an urgent need to understand the mechanisms of glioma tumorigenesis and develop or improve therapeutics. The aim of this study was to assess the possible prognostic value of cyclin-dependent kinase 6 (CDK6) and the effects of microRNA-495 (miR-495) manipulation on CDK6 expression and cell survival in glioma cells. Methods: Analyses of clinical specimens from GBM patients were used. Expression of CDK6 was analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. Expression of CDK6 was also analyzed after over-expression of miR-495 in T98 cells; both cell proliferation and RB phosphorylation were examined. Cell proliferation, cell cycle distribution, and RB phosphorylation were also examined after knockdown of CDK6 in U87-MG and T98 cells. Results: Analyses of clinical specimens from GBM patients identified that CDK6 is significantly expressed in gliomas. CDK6 antigen expression was higher in tumor cores and margins than in adjacent normal brain tissues, and higher levels of CDK6 expression in the tumor margin correlated with decreased survival. Over-expression of miR-495 in T98 cells downregulated the expression of CDK6 and inhibited retinoblastoma phosphorylation, and knockdown of CDK6 in U87-MG and T98 cells by siRNAs resulted in cell cycle arrest at the G1/S transition and inhibition of cell proliferation. Conclusions: This study revealed miR-495 is down-regulated in glioma tissues. Furthermore, miR-495 regulated CDK6 expression and involved in glioma cell growth inhibition, which indicated the possible role of miR-495 in tumor progression.

via World Journal of Surgical Oncology

Targeting PI3K/Akt represses Hypoxia inducible factor-1alpha activation and sensitizes Rhabdomyosarcoma and Ewing's sarcoma cells for apoptosis

Background: Hypoxia inducible factor alpha (HIF-1alpha) has been identified as an important novel target in apoptosis resistance of pediatric tumors such as Rhabdomyosarcoma (RMS) and Ewing's sarcoma (ES). Evidence suggests that PI3K/Akt signaling plays a role in regulation of HIF-1alpha activation as well as apoptosis resistance in various adult tumors. However the relevance of PI3K/Akt signaling in HIF-1alpha activation and apoptosis resistance in childhood tumors has not been addressed yet. Thus, this study was to investigate whether PI3K/Akt signaling is involved in hypoxia induced activation of HIF-1alpha as well as in resistance to hypoxia-induced apoptosis in childhood tumors such as RMS and ES. Methods: Constitutive activation of PI3K/Akt signaling was analyzed by Western blotting. Hypoxic activation of HIF-1alpha was determined by Western Blot analysis and electrophoretic mobility shift assay. Apoptosis was determined by flow cytometric analysis of the propidium iodine stained nuclei of cells treated with PI3K inhibitor LY294002 in combination with either TNF-related apoptosis-inducing ligand (TRAIL) or doxorubicin. Results: This study demonstrated that PI3K/Akt signaling was constitutively activated in RMS and ES cell lines, A204 and A673, respectively. Targeting PI3K/Akt signaling by the inhibitor LY294002 (30 muM) significantly decreased the protein expression as well as DNA binding activity of HIF-1alpha and restored the apoptosis-inducing ability of cells in hypoxia Additionally, pretreatment with LY294002 sensitized A204 and A673 cells to TRAIL or doxorubicin induced apoptosis under hypoxia. Conclusion: These results suggest that the constitutively active PI3K/Akt signaling contributes to hypoxic activation of HIF-1alpha as well as HIF1alpha-mediated apoptosis resistance in RMS and ES cells under hypoxia.

via Cancer Cell International

Dose-intense chemotherapy not superior for B-cell lymphoma

Compressing R-CHOP treatment cycles does not improve the outcome of elderly patients with diffuse large B-cell lymphoma, suggests research published in The Lancet Oncology.

via Med Wire News

Transmural invasion of hepatic flexure of colon causing cholecystocolic fistula by aggressive gallbladder carcinoma

Spontaneous enterobiliary fistulae are a complication of biliary disease or a disease of adjacent structures. Cholecystocolic fistulae are rare in relation to gallbladder carcinoma (GBC). Previous reports have presented images showing subtle findings suggestive of cholecystocolic fistula. We report the unusual spread and rare images of a case of cholecystocolicfistula,to highlight the aggressive nature of GBC and findings of gross transmural invasion of the colonic wall. The images acquired in all three planes define the anatomical and pathological extent conclusively. There are a higher number of GBC cases across the geographic belt of North India compared to the West. In this case, the patient's pathology was extensive and unresectable, and therefore palliative and supportive care wasadvised.

via World Journal of Surgical Oncology

Azacitidine might be beneficial in a subgroup of older AML patients compared to intensive chemotherapy: a single centre retrospective study of 227 consecutive patients

Background: Treatment options in older acute myeloid leukaemia (AML) patients include intensive chemotherapy, best supportive care (BSC), and hypomethylating agents. Currently, limited data is available on hypomethylating agents in older AML patients in unselected patient populations. Methods: To compare the effectiveness of azacitidine with conventional therapy, we collected data of 227 consecutive AML patients (>=60 years) who were treated with azacitidine (N = 26), intensive chemotherapy (N = 90), and BSC (N = 97). Results: Azacitidine-treated patients were older and had more comorbidities, but lower white blood cell- and bone marrow blast counts compared with intensive chemotherapy patients. Complete or partial response was achieved in 42% of azacitidine-treated patients and in 73% of intensive chemotherapy patients (P = 0.005). However, the overall survival (OS) was similar (1-year-OS 57% versus 56%, P = 0.93; 2-year-OS 35% versus 35%, P = 0.92), and remained similar after correction for risk factors in a multivariate analysis. Patients treated with BSC had an inferior OS (1-year- and 2-year-OS 16% and 2%, P < 0.001). Compared to intensive chemotherapy, azacitidine-treated patients spent less days in the hospital (0.5 versus 56, P < 0.001), and needed less red blood cell and platelet transfusions (2.7 versus 7, P < 0.001 and 0.3 versus 5, P < 0.001) in the first three months. Conclusions: Azacitidine treatment is associated with a comparable OS but higher tolerability in a subgroup of older AML patients compared with intensive chemotherapy. Patients receiving BSC had a poor prognosis.

via Journal of Hematology & Oncology

Li Fraumeni syndrome, cancer and senescence: a new hypothesis

Li Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome characterized by germline mutations in the TP53 tumour suppressor gene. Sufferers are prone to early onset cancers, particularly sarcomas, adrenocortical carcinoma and breast cancer. Cells from LFS sufferers are known to exhibit telomere dysfunction, genomic instability and spontaneous immortalisation. It is hypothesized that these facets of the LFS host are evidence that the host environment is "primed" for carcinogenesis over and above the lack of p53 tumour suppressor function. Further, it is hypothesized that the host presents an ideal environment for "two compartment tumour metabolism" to take place. Evidence from recent studies supports this new view of LFS and suggests that disrupting certain features of the host environment may markedly reduce the incidence of cancer in LFS sufferers.

via Cancer Cell International

Iron deficiency significance in cancer questioned

Researchers have uncovered an intriguing correlation between iron deficiency in patients with cancer and an increased likelihood of advanced disease and poor performance status.

via Med Wire News

Heart surgery risk in radiation-treated cancer survivors

Cancer survivors who are treated with chest radiation are nearly twice as likely to die in the years following major heart surgery as patients undergoing similar surgery who are never treated with radiation, a study shows.

via Med Wire News

Pulmonary sclerosing hemangioma: a unique epithelial neoplasm of the lung (report of 26 cases)

Background: Pulmonary sclerosing hemangioma (SH) is an uncommon tumor. The aim of this study was to identify the origin of pulmonary SH and summarize its clinicopathologic features.

via World Journal of Surgical Oncology

Follicular squamous cell carcinoma rates ‘underestimated’

Rates of follicular squamous cell carcinomas are underestimated, suggest results from a study published in the British Journal of Dermatology.

via Med Wire News

Irsogladine helps limit chemotherapy-induced oral mucositis

Irsogladine maleate is a promising drug for the management of oral mucositis in patients undergoing 5-fluorouracil-based chemotherapy, results of a randomized placebo-controlled trial indicate.

via Med Wire News

PSA test harms outweigh prostate cancer benefits in majority

Men should be warned that the chances of harm from screening with the prostate-specific antigen test outweigh the likelihood of benefit for most men, says the American College of Physicians in a guideline statement on prostate cancer screening.

via Med Wire News

The serum levels of the cytokines involved in the Th17 and Th1 cell commitment are increased in individuals with borderline thrombocytopenia

The definition of immune Thrombocytopenia (ITP) as a peripheral blood platelet count less than 100 x 109/L instead of the historical criteria of 150 x 109/L renders subjects with platelets between 100 and 150 x 109/L without a diagnosis. Here, we demonstrated that these subjects have enhanced levels of proinflammatory cytokines linked to Th1 and Th17 cell response, and are more frequently carriers of polymorphisms in genes that code cytokines involved in the commitment of Th1 and Th17 immune response, when compared with controls, similarly to that observed in patients with ITP.

via Journal of Hematology & Oncology

MEK and the inhibitors: from bench to bedside

Four distinct MAP kinase signaling pathways involving 7 MEK enzymes have been identified. MEK1 and MEK2 are the prototype members of MEK family proteins. Several MEK inhibitors are in clinical trials. Trametinib is the first one approved by FDA for the treatment of metastatic melanoma with BRAF V600 mutation. Selumetinib has been studied in combination with docetaxel in phase II randomized trial in previously treated patients with advanced lung cancer. Selumetinib group had better response rate and progression-free survival. This review also summarized new MEK inhibitors in clinical development, including pimasertib, refametinib, PD-0325901, TAK733, MEK162 (ARRY 438162), RO5126766, WX-554, RO4987655 (CH4987655), GDC-0973 (XL518), and AZD8330.

via Journal of Hematology & Oncology

Aggressive treatment rates low in bladder cancer

Aggressive treatment for muscle-invasive bladder cancer (MIBC) could be being underused, according to a US study that assessed its use among almost 30,000 patients.

via Med Wire News

Notch1 signaling is involved in regulating Foxp3 expression in T-ALL

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy. Immune tolerance induced by CD4+CD25+ regulatory T cells (Tregs) with high expression of Foxp3 is an important hypothesis for poor therapy response. Notch1 signaling is thought to be involved in the pathogenesis of this disease. Crosstalk between Notch and Foxp3+Tregs induced immune tolerance is unknown in T-ALL. We studied Foxp3 and Notch1 expression in vivo and in vitro, and analyzed the biological characteristics of T-ALL cell line systematically after Notch inhibition and explored the crosstalk between Notch signaling and Foxp3 expression. Methods: In vivo, we established T-ALL murine model by Jurkat cells transplantation to severe combined immunodeficiency (SCID) mice. Notch1 and Foxp3 expression was detected. In vitro, we used gamma-secretase inhibitor N-S-phenyl-glycine-t-butyl ester (DAPT) to block Notch1 signaling in Jurkat cells. Notch1, Hes-1 and Foxp3 genes and protein expression were detected by PCR and western blotting, respectively. The proliferation pattern, cell cycle and viability of Jurkat cells after DAPT treatment were studied. Protein expression of Notch1 target genes including NF-kappaB, p-ERK1/2 and STAT1 were determined. Results: We show that engraftment of Jurkat cells in SCID mice occurred in 8 of 10 samples (80%), producing disseminated human neoplastic lymphocytes in PB, bone marrow or infiltrated organs. Notch1 and Foxp3 expression were higher in T-ALL mice than normal mice. In vitro, Jurkat cells expressed Notch1 and more Foxp3 than normal peripheral blood mononuclear cells (PBMCs) in both mRNA and protein levels. Blocking Notch1 signal by DAPT inhibited the proliferation of Jurkat cells and induced G0/G1 phase cell cycle arrest and apoptosis. Foxp3 as well as p-ERK1/2, STAT1 and NF-kappaB expression was down regulated after DAPT treatment. Conclusions: These findings indicate that regulation of Foxp3 expression does involve Notch signaling, and they may cooperatively regulate T cell proliferation in T-ALL.

via Cancer Cell International

Preventive effect of ulinastatin on postoperative complications, immunosuppression, and recurrence in esophagectomy patients

Background: To evaluate the potential efficacy of preventive effect of ulinastatin in esophagectomy patients. Methods: Eighty patients with esophageal cancer were preoperatively allocated at random into two equal groups. Ulinastatin was administered to the treatment group (U) whereas the control group (C) received a placebo. The arterial oxygen tension and carbon dioxide tension were measured and the respiratory index (RI) was calculated. Plasma levels of circulating T lymphocyte subsets and interleukin 6 (IL-6) were measured and clinical courses of patients in the two groups were compared. Results: RI in the U group was significantly lower than that in the C group. The rate of postoperative complications and the duration of ICU stay were significantly lower in the U group. Ulinastatin significantly increased the rate of CD3+ and CD4+ cells, and ratio of CD4+/CD8+, but decreased the rate of CD8+ cells and release of IL-6 compared to the C group on postoperative days 1 and 3. Patients within the C group showed worse recurrence free survival. Multivariate analysis revealed that ulinastatin administration significantly decreased the incidence of recurrence. Conclusions: Ulinastatin had a preventive effect on postoperative complications and immunosuppression in esophagectomy patients, thereby prolongingrecurrence free survival.

via World Journal of Surgical Oncology

Decline linked to poor colorectal cancer chemotherapy outcomes in elderly

Severe toxicity and unexpected hospitalization among elderly patients receiving first-line chemotherapy for metastatic colorectal cancer is predicted by factors such as cognitive function and impairments in autonomy, say French scientists.

via Med Wire News

Metabolomics model improves pancreatic cancer diagnosis

Researchers have developed a diagnostic model for pancreatic cancer that can detect resectable cancer at an early stage and discriminate cancer from chronic pancreatitis.

via Med Wire News

Response to microtubule-interacting agents in primary epithelial ovarian cancer cells

Background: Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. Methods: Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and alphabeta-tubulin and p53 status was also investigated. Results: All newly generated primary cancer cells were highly sensitive to the drugs. alphabeta-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients. Conclusions: The isolation and characterization of primary ovarian cancer cells from ovarian cancer patient's specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings.

via Cancer Cell International

Water-based exercise improves shoulder function for lymphedema patients

A water-based exercise program significantly improves shoulder range of motion in breast cancer survivors with lymphedema, report researchers.

via Med Wire News

Radiotherapy ‘does not preclude’ immediate breast reconstruction

Women who receive radiotherapy after free-flap breast reconstruction are no more likely to require revision surgery than those who do not, say US researchers who believe immediate autologous surgery is feasible in this group.

via Med Wire News

Patient age influences leukemia characteristics, treatment

Adult patients with acute lymphoblastic leukemia are more likely to require high-risk chemotherapy than their pediatric counterparts, demonstrate results from a study using standardized diagnostic, risk assessment and treatment protocols.

via Med Wire News

Hip replacement cancer risk ‘not major cause for concern’

Epidemiologic evidence may reassure patients with hip replacements that their prosthesis is unlikely to significantly increase their risk for cancer, UK researchers say.

via Med Wire News

Prognostic markers found for oropharyngeal cancer

Alcohol consumption and p16 expression are associated with prognosis in patients with oropharyngeal squamous cell carcinoma, Japanese researchers believe.

via Med Wire News

Parathyroid carcinoma in a 30-year-old man: a diagnostic and management challenge

Parathyroid carcinoma is a rare endocrine malignancy, accounting for less than 1% of cases of primary hyperparathyroidism. Patient-related factors such as age and sex, as well as the biological features and management of the cancer, influence mid-term and long-term survival. We report a case of a young man with an unusual presentation of parathyroid carcinoma. The patient presented with left thigh swelling, which had been present for 6 months without other symptoms of hypercalcemia. On computed tomography scan a hypodense lesion, 30 x 20 x 20 mm in size, was seen in the posterior thyroid. There was no evidence of cervical lymphadenopathy or local infiltration. On a Sestamibi scan, a hot spot was seen in the lower pole of left thyroid lobe. Cervical neck exploration was performed. The patient subsequently underwent surgery and a parathyroid tumor was excised. The tumor was adherent to the thyroid capsule, but there was no evidence of invasion. After surgery, the patient's calcium and parathyroid hormone levels normalized, but histology confirmed parathyroid carcinoma with capsular and vascular invasion. The patient was offered reoperation, but declined, and developed recurrent parathyroid carcinoma 2 years later. In this report, we aim to present the challenges in managing parathyroid carcinoma and discuss factors that might contribute to future locoregional recurrences. This case also highlighted several issues, including the challenge of ascertaining the diagnosis before surgery and the dilemma of reoperation after simple excision.

via World Journal of Surgical Oncology

Gene fusion reduces NSCLC patient survival

ROS1 fusions predict a poor outcome in Chinese patients with non-small-cell lung cancer, study findings suggest.

via Med Wire News

GPs' referral wording can speed up childhood cancer diagnosis

The wording of a general practitioner's referral letter to the consultant has a significant impact on the time to diagnosis for pediatric cancer patients, Danish research shows.

via Med Wire News

Marital status affects place of cancer death

Having a hematologic cancer or being single, widowed, or divorced, reduces cancer patients’ chances for dying at home or in a hospice, study findings show.

via Med Wire News

Reduced function in prostate cancer patients receiving radiotherapy

Men treated with a combination of intensity-modulated radiotherapy and androgen deprivation therapy for locally advanced prostate cancer suffer from long-term reductions in urinary, bowel, and sexual function, show study findings.

via Med Wire News

Activity of histone deacetylase inhibitors and an Aurora kinase inhibitor in BCR-ABL-expressing leukemia cells: Combination of HDAC and Aurora inhibitors in BCR-ABL-expressing cells

Background: The use of imatinib, an ABL tyrosine kinase inhibitor, has led to a dramatic change in the management of BCR-ABL-positive leukemia patients. However, resistance to imatinib mediated by mutations in the BCR-ABL domain has become a major problem in the treatment of these patients. Methods: In the present study, we examined the activity of histone deacetylase (HDAC) inhibitors in combination with an Aurora kinase inhibitor in BCR-ABL-expressing cells. Results: We found the HDAC inhibitors vorinostat and/or pracinostat (SB939) induced apoptosis in BCR-ABL-expressing cells. Additionally, HDAC inhibitors reduced levels of Aurora A and B protein. An Aurora kinase inhibitor, tozasertib (VX-680), inhibited growth, promoted pro-apoptotic activity, reduced the phosphorylation of BCR-ABL and Crk-L, and activated caspase-3 and poly (ADP-ribose) polymerase (PARP) in BCR-ABL-positive cells. Moreover, after treatment with tozasertib, HDAC protein expression was decreased. Combination of vorinostat or pracinostat with tozasertib had a synergistic inhibitory effect on the proliferation of T315I cells. Phosphorylation of Crk-L decreased, and PARP activation increased after treatment with vorinostat or pracinostat and tozasertib. Moreover, combination of vorinostat or pracinostat and tozasertib significantly increased the extent of apoptosis in primary chronic myeloid leukemia cells. Conclusions: This study demonstrated that combination of HDAC and Aurora inhibitors was highly effective against BCR-ABL-expressing cells.

via Cancer Cell International

Mesohepatectomy with total caudate lobectomy of the liver for hepatocellular carcinoma

Background: Mesohepatectomy with total resection of the caudate lobe and extrahepatic bile duct is sometimes performed for hilar cholangiocarcinoma or gallbladder carcinoma; however, only a few reports on mesohepatectomy with total caudate lobectomy of the liver for hepatocellular carcinoma are available. Methods: A 71-year-old woman was preoperatively diagnosed with hepatocellular carcinoma in the central bisections (Couinaud's segments 4, 5, and 8) and the paracaval portion of the caudate lobe. Mesohepatectomy with total caudate lobectomy of the liver permitted the removal of tumors to provide a cancer-free raw surface of the liver. Mobilization of the caudate lobe is an important procedure in this surgery. Before the liver parenchyma was dissected, all short hepatic veins were ligated and divided from the left to the right side as the left lateral section was retracted to the right, and the caudate lobe branches of the portal vein and hepatic artery were ligated and divided. After the liver parenchymal dissection, both between the left lateral and medial sections and between the right anterior and posterior sections, the Glissonean branches of the caudate lobe were ligated and divided as the central bisections were anteriorly retracted. Finally, liver parenchymal dissection was performed between the caudate lobe and the right posterior section, which was along the right side of the inferior vena cava. Results: The surgery time was 538 minutes and blood loss was 1,207 mL. No blood transfusions were required during or after surgery. The postoperative course was uncomplicated. The patient is still alive 25 months after hepatectomy. Conclusion: Although mesohepatectomy with total caudate lobectomy of the liver is technically more difficult than mesohepatectomy of the liver because the caudate lobe must be completely detached from the inferior vena cava and the hilar plate, it is a safe and effective treatment method in selected patients with hepatocellular carcinoma located at both the central bisections and the paracaval portion of the caudate lobe.

via World Journal of Surgical Oncology

Oral squamous cell carcinoma in relation to field precancerisation: pathobiology

Squamous cell carcinoma of the oral cavity evolves within a field of precancerized oral epithelium containing keratinocytes at different stages of transformation. Following acquisition of additional genetic alterations, these precancerous keratinocytes may become cancerous.Persons with apparently successfully treated oral squamous cell carcinoma are at high risk of developing a new carcinoma at, or close to the site of the treated tumour. This second carcinoma may have developed either from malignant keratinocytes left behind at surgery (recurrence), or from transformed keratinocytes within the field of precancerized epithelium from which the primary carcinoma had arisen (new carcinoma).The cells of the new carcinoma may have genetic changes in common with the cells of the original carcinoma because both are descended from a proliferating monoclone within the precancerized field; but if the new cancer originates from a different clone, it may have a dissimilar genetic profile even if the original and the new carcinoma are closely contiguous.The purpose of this article is to review the pathobiology of oral squamous cell carcinoma in relation to fields of precancerised oral epithelium.

via Cancer Cell International

Surveillance imaging ‘unjustified’ in rituximab-treated lymphoma

Surveillance fluorodeoxyglucose positron emission tomography delivers a high false-positive rate and has low specificity during follow up in diffuse large cell lymphoma patients treated with rituximab, a study shows.

via Med Wire News

T-cell therapy holds promise for ALL children

Two children with relapsed and chemotherapy-refractory pre-B-cell acute lymphoblastic leukemia achieved complete remission after treatment with modified T cells, show study findings published in TheNew England Journal of Medicine.

via Med Wire News

Hsp90 inhibitor shows NSCLC promise

Treatment with a heatshock protein 90 inhibitor may induce loss of EML4–AKL expression in non-small cell lung cancer cells, preliminary results suggest.

via Med Wire News

Presence of alternative lengthening of telomeres associated circular extrachromosome telomere repeats in primary leukemia cells of chronic myeloid leukemia

Background: The predominant mechanism by which human tumors maintain telomere length is via telomerase. In ~10% of tumor samples, however, telomere length is conserved, despite no detectable telomerase activity, in part through activation of the alternative lengthening of telomeres (ALT) pathway. Methods: We studied the circular extra-chromosomal telomeric repeat (ECTR), an ALT hallmark, and telomerase activity in 24 chronic myeloid leukemia (CML) patients in chronic phase (CP). Results: We identified the presence of ECTR in primary leukemia cells from some of these samples, which indicates the possible involvement of an ALT mechanism. Moreover, we found that some samples exhibited both circular ECTR and telomerase activities, suggesting that both mechanisms can contribute to the onset of CML. Conclusion: We propose that ALT or the combined activities of ALT and telomerase might be required for the early stages of leukemogenesis. These findings shed new light into the oncogenic pathways responsible for the maintenance of telomere length in leukemia, which will ultimately determine the effectiveness of anti-telomerase-based treatment protocols.

via Journal of Hematology & Oncology

Structurally differentiated cis-elements that interact with PU.1 are functionally distinguishable in acute promyelocytic leukemia

Background: Transcription factor PU.1, a member of the ETS family, is a master regulator of myeloid differentiation whose functional disruption is often associated with acute myeloid leukemia (AML). Although much has been learned about PU.1 over the past decades, relatively little is known about cis-elements that interact with this factor under physiological or pathological conditions, especially in the whole-genome scale. We aimed to define the cistrome of PU.1 in acute promyelocytic leukemia (APL) cells and characterize the cis-elements bound by PU.1. Methods: Chromatin immunoprecipitation with specific antibody coupled with deep sequencing (ChIP-seq) was used to investigate the in vivo PU.1 binding sites at the whole-genome scale in APL-derived NB4 cells. The ChIP-quantitative (q)-PCR and luciferase reporter assays were used to validate the binding events and trans-activity, respectively. Various computational analyses, including motif mining, evolutionary conservation analysis and functional enrichment analysis, were performed to characterize the cis-elements that interacted with PU.1. Results: A total of 26,907 significantly enriched binding regions of PU.1 were identified under the false discovery rate 0.1% in NB4 cells. PU.1 bound to various types of genomic regions and acted as a promoter-enhancer dual binding transcription factor. Based on the sequence length and composition, two types of representative motifs were identified in PU.1 binding sites: a long and a short motif. The long motif, characterized by high sequence specificity and binding affinity, predominantly resided in the promoter-distal regions. In contrast, the short one, with strong evolutionary constraint, represented the primary PU.1 cis-elements in the promoter-proximal regions. Interestingly, the short one showed more preference to be correlated with the binding of other factors, especially PML/RARalpha. Moreover, genes targeted by both PU.1 and PML/RARalpha were significantly involved in categories associated with oncogenesis, hematopoiesis and the pathogenesis of acute myeloid leukemia. Conclusions: Our results demonstrate that structurally differentiated cis-elements that interact with PU.1 are functionally distinguishable in APL, suggesting that the sequence diversity of cis-elements might be a critical mechanism by which cells interpret the genome, and contribute to distinct physiological and/or pathological function.

via Journal of Hematology & Oncology

Clinical utility of measuring expression levels of KAP1, TIMP1 and STC2 in peripheral blood of patients with gastric cancer

Background: We examined preoperative kinesin II-associated protein (KAP1), TIMP metallopeptidase inhibitor 1 (TIMP1) and stanniocalcin 2 (STC2) expression levels in patients with gastric cancers to assess their clinical application for diagnosing and monitoring diseases. Methods: Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of KAP1, TIMP1, STC2, talin 2 (TLN2), sushi-repeat-containing protein, X-linked 2 (SRPX2) and secreted protein, acidic, cysteine-rich (SPARC) in the patients' peripheral blood karyocytes. The data were analyzed with receiver operating characteristics (ROC) curves. Results: A total of 112 patients with gastric cancer, 42 patients with recurrence and 107 healthy volunteers were recruited. There were significant correlations between KAP1, TIMP1 and STC2 levels, and TNM tumor stages and distant metastases. The area under the ROC curves (AUC) of KAP1 was 0.803 +/- 0.040 (P = 0.0001), the AUC of TIMP1 was 0.767 +/- 0.043 (P = 0.0001) and the AUC of STC2 was 0.769 +/- 0.045 (P = 0.0001), thus differentiating preoperative gastric cancer patients from healthy volunteers by ROC curve analysis. The AUC of STC2 was 0.739 +/- 0.070 (P = 0.004) and the AUC of KAP1 was 0.418 +/- 0.088 (P = 0.319), thus differentiating recurrence of gastric cancer from healthy volunteers by ROC curve analysis. High TIMP1 and STC2 expression levels were suspected to be poor prognostic factors of disease recurrence in patients with gastric cancer. Conclusions: KAP1, TIMP1 and STC2 expression levels may be potential biomarkers for the screening, diagnosis, prognosis and surveillance of gastric cancer.

via World Journal of Surgical Oncology