A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Neoplasms - Top 30 Publications

Midostaurin in FLT3-Mutated Acute Myeloid Leukemia.

Midostaurin in FLT3-Mutated Acute Myeloid Leukemia.

Adjuvant Melanoma Therapy - Head-Spinning Progress.

Midostaurin in FLT3-Mutated Acute Myeloid Leukemia.

A Pilot Study of the Prevalence of Anal Human Papillomavirus and Dysplasia in a Cohort of Patients With IBD.

Defective cell-mediated immunity increases the risk of human papillomavirus-associated anal dysplasia and cancer. There is limited information on anal canal disease in patients with IBD.

Naples Prognostic Score, Based on Nutritional and Inflammatory Status, is an Independent Predictor of Long-term Outcome in Patients Undergoing Surgery for Colorectal Cancer.

The existing scores reflecting the patient's nutritional and inflammatory status do not include all biomarkers and have been poorly studied in colorectal cancers.

Initiation of a Transanal Total Mesorectal Excision Program at an Academic Training Program: Evaluating Patient Safety and Quality Outcomes.

Short-term results have shown that transanal total mesorectal excision is safe and effective for patients with mid to low rectal cancers. Transanal total mesorectal excision is considered technically challenging; thus, adoption has been limited to a few academic centers in the United States.

Nodal Disease in Rectal Cancer Patients With Complete Tumor Response After Neoadjuvant Chemoradiation: Danger Below Calm Waters.

A subset of patients with rectal cancer who undergo neoadjuvant chemoradiation therapy will develop a complete pathologic tumor response. Complete nodal response is not universal in these patients and is difficult to assess clinically. Quantifying the risk of nodal disease would allow for targeted therapy with either radical resection or "watchful waiting."

Is the Distance Worth It? Patients With Rectal Cancer Traveling to High-Volume Centers Experience Improved Outcomes.

It is unclear whether traveling long distances to high-volume centers would compensate for travel burden among patients undergoing rectal cancer resection.

Do Moderate Surgical Treatment Delays Influence Survival in Colon Cancer?

Studies examining treatment delay and survival after surgical treatment of colon cancer have varied in quality and outcome, with little evidence available regarding the safety of longer surgical treatment wait times.

Genetic variants of SULT1A1 and XRCC1 genes and risk of lung cancer in Bangladeshi population.

Lung cancer is one of the most frequently occurring cancers throughout the world as well as in Bangladesh. This study aimed to correlate the prognostic and/or predictive value of functional polymorphisms in SULT1A1 (rs9282861) and XRCC1 (rs25487) genes and lung cancer risk in Bangladeshi population. A case-control study was conducted which comprises 202 lung cancer patients and 242 healthy volunteers taking into account the age, sex, and smoking status. After isolation of genomic DNA, genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method and the lung cancer risk was evaluated as odds ratio that was adjusted for age, sex, and smoking status. A significant association was found between SULT1A1 rs9282861 and XRCC1 rs25487 polymorphisms and lung cancer risk. In case of rs9282861 polymorphism, Arg/His (adjusted odds ratio = 5.06, 95% confidence interval = 3.05-8.41, p < 0.05) and His/His (adjusted odds ratio = 3.88, 95% confidence interval = 2.20-6.82, p < 0.05) genotypes were strongly associated with increased risk of lung cancer in comparison to the Arg/Arg genotype. In case of rs25487 polymorphism, Arg/Gln heterozygote (adjusted odds ratio = 4.57, 95% confidence interval = 2.79-7.46, p < 0.05) and Gln/Gln mutant homozygote (adjusted odds ratio = 4.99, 95% confidence interval = 2.66-9.36, p < 0.05) were also found to be significantly associated with increased risk of lung cancer. This study demonstrates that the presence of His allele and Gln allele in case of SULT1A1 rs9282861 and XRCC1 rs25487, respectively, involve in lung cancer prognosis in Bangladeshi population.

Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer.

Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.

MicroRNA-target cross-talks: Key players in glioblastoma multiforme.

The role of microRNAs in brain cancer is still naive. Some act as oncogene and others as tumor suppressors. Discovery of efficient biomarkers is mandatory to debate that aggressive disease. Bioinformatically selected microRNAs and their targets were investigated to evaluate their putative signature as diagnostic and prognostic biomarkers in primary glioblastoma multiforme. Expression of a panel of seven microRNAs (hsa-miR-34a, hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, hsa-miR-326, and hsa-miR-375) and seven target genes ( E2F3, PI3KCA, TOM34, WNT5A, PDCD4, DFFA, and EGFR) in 43 glioblastoma multiforme specimens were profiled compared to non-cancer tissues via quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry staining for three proteins (VEGFA, BAX, and BCL2) was performed. Gene enrichment analysis identified the biological regulatory functions of the gene panel in glioma pathway. MGMT ( O-6-methylguanine-DNA methyltransferase) promoter methylation was analyzed for molecular subtyping of tumor specimens. Our data demonstrated a significant upregulation of five microRNAs (hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, and hsa-miR-375), three genes ( E2F3, PI3KCA, and Wnt5a), two proteins (VEGFA and BCL2), and downregulation of hsa-miR-34a and three other genes ( DFFA, PDCD4, and EGFR) in brain cancer tissues. Receiver operating characteristic analysis revealed that miR-34a (area under the curve = 0.927) and miR-17 (area under the curve = 0.900) had the highest diagnostic performance, followed by miR-221 (area under the curve = 0.845), miR-21 (area under the curve = 0.836), WNT5A (area under the curve = 0.809), PDCD4 (area under the curve = 0.809), and PI3KCA (area under the curve = 0.800). MGMT promoter methylation status was associated with high miR-221 levels. Moreover, patients with VEGFA overexpression and downregulation of TOM34 and BAX had poor overall survival. Nevertheless, miR-17, miR-221, and miR-326 downregulation were significantly associated with high recurrence rate. Multivariate analysis by hierarchical clustering classified patients into four distinct groups based on gene panel signature. In conclusion, the explored microRNA-target dysregulation could pave the road toward developing potential therapeutic strategies for glioblastoma multiforme. Future translational and functional studies are highly recommended to better understand the complex bio-molecular signature of this difficult-to-treat tumor.

Beta-mangostin from Cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G0/G1 cell-cycle arrest.

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G0/G1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G0/G1 phase and prompted the intrinsic apoptosis pathway.

Establishment of cholangiocarcinoma cell lines from patients in the endemic area of liver fluke infection in Thailand.

Cholangiocarcinoma is a rare type of cancer which is an increasingly discernible health threat. The disease is usually very difficult in diagnosis and various treatment modalities are typically not effective. Cholangiocarcinoma is a complex and very heterogeneous malignancy characterized by tumor location, different risk factors, molecular profiling, and prognosis. Cancer cell lines represent an important tool for investigation in various aspects of tumor biology and molecular therapeutics. We established two cell lines, KKU-452 and KKU-023, which were derived from patients residing in the endemic area of liver fluke infection in Thailand. Both of tumor tissues have gross pathology of perihilar and intrahepatic mass-forming cholangiocarcinoma. Two cell lines were characterized for their biological, molecular and genetic properties. KKU-452 and KKU-023 cells are both adherent cells with epithelium morphology, but have some differences in their growth pattern (a doubling time of 17.9 vs 34.8 h, respectively) and the expression of epithelial bile duct markers, CK7 and CK19. Cytogenetic analysis of KKU-452 and KKU-023 cells revealed their highly complex karyotypes; hypertriploid and hypotetraploid, respectively, with multiple chromosomal aberrations. Both cell lines showed mutations in p53 but not in KRAS. KKU-452 showed a very rapid migration and invasion properties in concert with low expression of E-cadherin and high expression of N-cadherin, whereas KKU-023 showed opposite characters. KKU-023, but not KKU-452, showed in vivo tumorigenicity in xenografted nude mice. Those two established cholangiocarcinoma cell lines with unique characters may be valuable for better understanding the process of carcinogenesis and developing new therapeutics for the patients.

Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

Castration-Resistant Prostate Cancer: An Algorithmic Approach.

Since 2010, 5 new agents have been approved for advanced prostate cancer treatment. The American Urologic Association (AUA) published guidelines for the management of castration-resistant prostate cancer in 2013. These guidelines identify 6 index patients to consider when selecting the most appropriate treatment. No comparative trials have provided an approach to optimize the sequencing of these drugs. For the urologist, incorporating the guidelines into clinical practice typically requires a multidisciplinary team. This article provides an algorithmic approach based on indication and mechanism of action that complements the AUA guidelines to ensure patients receive the most optimal care.

Approach to the Patient with High-Risk Prostate Cancer.

Men classified as having high-risk prostate cancer warrant treatment because durable outcomes can be achieved. Judicious use of imaging and considerations of risk factors are essential when caring for men with high-risk disease. Radical prostatectomy, radiation therapy, and androgen deprivation therapy all play pivotal roles in the management of men with high-risk disease, and potentially in men with metastatic disease. The optimal combinations of therapeutic regimens are an evolving area of study and future work looking into therapies for men with high-risk disease will remain critical.

The Role of Local Therapy for Oligometastatic Prostate Cancer: Should We Expect a Cure?

The role of local treatment in oligometastatic prostate cancer remains contentious. Treatment of the prostate in metastatic disease may confer benefit, but prospective data are lacking. With improvements in treatments, aggressive strategies directed at metastases have increasingly become of clinical interest. Current evidence suggests good local control can be achieved; however, further data are required to determine overall cancer outcomes. This article evaluates the evidence available and consider whether local treatment of oligometastatic disease is a feasible, safe, and a positive strategy in this disease cohort. Cure should not be expected, although prolonged disease and treatment-free survival may be observed.

Newly Diagnosed Metastatic Prostate Cancer: Has the Paradigm Changed?

Androgen deprivation therapy (ADT) has been conventional treatment of newly diagnosed metastatic prostate cancer for more than 70 years. However, all patients eventually become castration-resistant and a significant proportion of life span is spent in the castration-resistant state. Prospective randomized control trials have incorporated early chemotherapy along with ADT based on the hypothesis that a significant level of resistance to ADT already exists in newly diagnosed metastatic prostate cancer and ADT exhibits synergistic antitumor activity with taxanes. We discuss the changing landscape of management of patients with newly diagnosed metastatic prostate cancer based on recently published landmark randomized trials.

Managing Cancer Relapse After Radical Prostatectomy: Adjuvant Versus Salvage Radiation Therapy.

An increasing proportion of men are undergoing radical prostatectomy for locally advanced prostate cancer. More than half of men with adverse pathologic features are expected to experience disease recurrence within 10 years. This article discusses the use of postoperative radiation therapy to decrease this risk. Evidence from 3 randomized trials and multiple retrospective studies indicates that either adjuvant or salvage radiation improve biochemical progression-free survival and may improve overall survival. Novel imaging and genomic analysis can improve patient selection for either modality, however current tests are unable to identify all patients who may benefit from additional local therapy.

Extent of Lymphadenectomy at Time of Prostatectomy: An Evidence-Based Approach.

Pelvic lymph node dissection (PLND) at the time of radical prostatectomy is the most accurate method of lymph node staging in prostate cancer. Although there are varied practices in anatomic extent of PLND, evidence favors an extended PLND (ePLND) including external iliac, obdurator, and internal iliac nodes. Removing presacral and/or common iliac nodes to the ureteric crossing can improve staging. The oncologic benefits of extended dissection are unclear based on methodologic limitations and bias in the available evidence. Diverse nomograms may clarify which patients warrant ePLND. Higher level evidence is needed to clarify the therapeutic effects of ePLND and who benefits most.

Focal Ablation of Early-Stage Prostate Cancer: Candidate Selection, Treatment Guidance, and Assessment of Outcome.

Prostate cancer lesions smaller than 0.5 m(3), or Gleason pattern 3, are likely clinically insignificant. Clinically significant disease is often limited to a single index lesion. Focal ablation targets this index lesion, maintains oncological control, and minimizes complications by preserving healthy prostate tissue. Template mapping biopsy or multiparametric MRI-targeted biopsies are used to identify appropriate index lesions. Multiple energy modalities have been tested, including high-intensity frequency ultrasound, cryoablation, laser ablation, photodynamic therapy, focal brachytherapy, radiofrequency ablation, irreversible electroporation. Outcome is assessed by biopsy of the target area, triggered by prostate-specific antigen measurements or MRI imaging, or performed per protocol at 12 months.

Contemporary Active Surveillance: Candidate Selection, Follow-up Tools, and Expected Outcomes.

This article is a summary of the rationale for conservative management, the molecular biology of low-grade cancer, the principles of management, the expected outcome of surveillance, unanswered questions, and research opportunities.

(68)Gallium-Prostate-Specific Membrane Antigen PET/Computed Tomography for Primary and Secondary Staging in Prostate Cancer.

Prostate-specific membrane antigen (PSMA) PET has been recently introduced for the diagnosis of patients with metastatic prostate cancer (PCa). Until today, staging of patients with PCa relied mostly on morphologic features, such as size or shape, resulting in low detection rates in disease recurrence. PSMA PET imaging provides molecular information and, in combination with conventional imaging, offers improved sensitivity and specificity. This review discusses the benefits and limitations of PSMA imaging in the setting of primary staging and detection of recurrent disease in comparison with standard-of-care imaging techniques.

Whom to Treat: Postdiagnostic Risk Assessment with Gleason Score, Risk Models, and Genomic Classifier.

Management of prostate cancer presents unique challenges because of the disease's variable natural history. Accurate risk stratification at the time of diagnosis in clinically localized disease is crucial in providing optimal counseling about management options. To accurately distinguish pathologically indolent tumors from aggressive disease, risk groups are no longer sufficient. Rather, multivariable prognostic models reflecting the complete information known at time of diagnosis offer improved accuracy and interpretability. After diagnosis, further testing with genomic assays or other biomarkers improves risk classification. These postdiagnostic risk assessment tools should not supplant shared decision making, but rather facilitate risk classification and enable more individualized care.

Prediagnostic Risk Assessment with Prostate MRI and MRI-Targeted Biopsy.

Prostate MRI is commonly used in the detection of prostate cancer to reduce the detection of clinically insignificant disease; maximize the detection of clinically significant cancer; and better assess disease size, grade, and location. The clinical utility of MRI seems to apply to men with no prior biopsy, who have had a previous negative biopsy, and men who are candidate for active surveillance. In conjunction with traditional clinical parameters and secondary biomarkers, MRI may allow more accurate risk stratification and assessment of need for prostate biopsy.

How to Biopsy: Transperineal Versus Transrectal, Saturation Versus Targeted, What's the Evidence?

Until recently, prostate biopsy for the detection of prostate cancer has been performed transrectally and in an untargeted sampling fashion. Consequently, the procedure has suffered a small but significant risk of severe morbidity through infection, and low diagnostic accuracy, with undergrading and missed diagnosis being common. MRI is revolutionizing prostate cancer diagnosis by improving detection accuracy via targeted biopsy. Transperineal biopsy is eradicating sepsis as a risk of prostate biopsy, while avoiding the need for broad-spectrum or combination prophylactic antibiotics. This article analyzes the data on the various current methods of performing prostate biopsy and recommends an optimal technique.

Whom to Biopsy: Prediagnostic Risk Stratification with Biomarkers, Nomograms, and Risk Calculators.

This article describes markers used for prostate biopsy decisions, including prostrate-specific antigen (PSA), free PSA, the prostate health index, 4Kscore, PCA3, and ConfirmMDx. It also summarizes the use of nomograms combining multiple variables for prostate cancer detection.

Biomarker MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma Identified Based on Gene Expression Data and MicroRNA-mRNA Network Analysis.

Oral squamous cell carcinoma is one of the most malignant tumors with high mortality rate worldwide. Biomarker discovery is critical for early diagnosis and precision treatment of this disease. MicroRNAs are small noncoding RNA molecules which often regulate essential biological processes and are good candidates for biomarkers. By integrative analysis of both the cancer-associated gene expression data and microRNA-mRNA network, miR-148b-3p, miR-629-3p, miR-27a-3p, and miR-142-3p were screened as novel diagnostic biomarkers for oral squamous cell carcinoma based on their unique regulatory abilities in the network structure of the conditional microRNA-mRNA network and their important functions. These findings were confirmed by literature verification and functional enrichment analysis. Future experimental validation is expected for the further investigation of their molecular mechanisms.