Current Issue : October - December Volume : 2019 Issue Number : 4 Articles : 5 Articles
Background. For childhood acute lymphocytic leukemia (ALL), central nervous system leukemia (CNSL) is still themain reason of\ntreatment failure. Changes of cerebrospinal fluid (CSF) proteome are deemed to occur after intrathecal chemotherapy. Objective.\nTo find critical CSF biomarkers, which could be utilized to increase diagnostic and prognostic accuracy of CNSL. Methods. We\nperformed proteomic profiling of CSF before and after the treatment of six sporadic paediatric patients diagnosed as ALL with\ncentral nervous system (CNS) involvement. CSF samples were properly processed and analyzed through the use of label-free liquid\nchromatography-tandem mass spectrometry (LC-MS/MS). Results. Among identified 428 unique proteins in all CSF samples, we\nquantified 10 altered proteins with diverse biological functions after induction chemotherapy. Conclusions. The levels of those 10\nproteins change during the treatment of CNSL. Some of the proteins are likely to play a vital biological role as biomarkers for the\ndevelopment of ALL. In addition, our results indicated the feasible and reproducible utility of CSF for diagnosis and prognosis of\npatients with CNSL....
Abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed\ncancer worldwide. Despite advances in the treatment management, locally advanced disease has a\npoor prognosis, with a 5-year survival rate of approximately 50%. The growth of HNSCC is\nmaintained by a population of cancer stem cells (CSCs) which possess unlimited self-renewal\npotential and induce tumor regrowth if not completely eliminated by therapy. The population of\nCSCs is not only a promising target for tumor treatment, but also an important biomarker to identify\nthe patients at risk for therapeutic failure and disease progression. This review aims to provide an\noverview of the recent pre-clinical and clinical studies on the biology and potential therapeutic\nimplications of HNSCC stem cells....
Introduction. Ampullary cancers represent a subset of periampullary cancers, comprising only 0.2% all gastrointestinal cancers.\nLocalized disease is primarily managed by a surgical intervention, called pancreaticoduodenectomy (PD), followed in many\ncases by the administration of adjuvant chemotherapy (CT) or chemoradiation therapy (CRT). However, there are no clear\nevidence-based guidelines to aid in selecting both the modality and regimen of adjuvant therapy for resected Ampullary\ncarcinoma. Methods. We retrospectively analyzed 54 patients at KU Cancer Center, who had undergone endoscopic resection or\npancreatic oduodenectomy (PD) for Ampullary cancer from June 2006 to July 2016.We obtained patientsâ?? baseline characteristics,\nclinical presentation, pathology, treatment modality, recurrence pattern, and survival outcomes. The time-to-events data were\ncompared using Kaplan-Meier methods. A univariate and multivariate Cox proportional hazards regression was performed to\nevaluate factors associated with overall survival (OS) and generate hazard ratios (HR). Results.The mean age of the 54 patients\nwas 68 (37-90). 38 (70%) were males and 16 (30%) were females. Most of the patients were Caucasian (76%). Approximately\nhalf of all patients had a history of smoking, 20% had alcohol abuse, and 13% had pancreatitis. Among the 54 patients\nwith localized cancers, 9 (16%) were treated definitively with nonoperative therapies, usually due to a prohibitive comorbidity\nprofile, performance status, or unresectable tumor. 45 out of 54 patients (83%) underwent surgery. Of the 45 patients who\nunderwent surgery, 18 patients (40% of the study cohort) received adjuvant therapy due to concerns for advanced disease as\ndetermined by the treating physician. 13 patients (24%) received adjuvant CT and 5 patients (9.2%) received CRT. The remaining\n27 patients (50%) underwent surgery alone. The median OS for the entire study cohort was 30 months. When compared to\nsurgery alone, adjuvant therapy with either CT or CRT had no statistically significant difference in terms of progression-free\nsurvival (p=0.56) or overall survival (p=0.80). In univariate Cox proportional hazards regression analysis, high-risk features\nlike peripancreatic extension (16%) and perineural invasion (26%) were found to be associated with poor OS. Lymph node\nmetastasis (29%) did not significantly affect OS (HR 1.42, 95% CI [0.73-1.86]; p=0.84). Lymphovascular invasion (29%) was not\nassociated with poor OS (HR 1.22, 95% CI [0.52, 2.96]; p=0.76). In multivariate Cox regression analysis, only age group>70\nyears was significantly associated with OS , while other factors, including the receipt of adjuvant therapy, lymph nodes, positive\nmargin, and lymphovascular, perineural, and peripancreatic involvement, were not significantly associated with OS. These\nresults are likely due to small sample size. Conclusions. Despite numerous advances in both cancer care and research, efforts\nin rare malignancies such as Ampullary cancer remain very challenging with a clear lack of an evidence-based standard of\ncare treatment paradigm. Although adding adjuvant therapies such as chemotherapy or chemoradiotherapy is likely to improve\nsurvival in high-risk disease, there is no standardized regimen for the treatment of Ampullary cancer.More research is required to\nelucidate whether statistically and clinically relevant differences exist that may warrant a change in the current adjuvant treatment\nstrategies....
Acute lymphoblastic leukemia and other aggressive lymphoid malignancies like Burkitt leukemia/lymphoma have high incidence\nof central nervous system(CNS) involvement. Various solid tumors, most notably breast cancer, can also metastasize into the CNS\nas a late stage complication causing devastating effects. Intrathecal (IT) chemotherapy consisting of methotrexate, cytarabine, or\nthe two in combination is frequently used for the prophylaxis and treatment of CNSmetastasis. Because of the high toxicity of these\nchemotherapeutic agents, however, their side effect profiles are potentially catastrophic.The incidence of neurotoxicity secondary\nto IT chemotherapy is well defined in the pediatric literature but is poorly reported in adults. Here, we investigated the incidence\nof neurologic and nonneurologic side effects secondary to IT chemotherapy in 109 consecutive adult patients over a two-year time\nperiod at hospitals associated with our institution. Of 355 IT chemotherapy treatments received by these patients, 11 (3.10%) resulted\nin paresthesias or paralysis, which we defined as significant neurologic events in our analysis.We also examined minor events that\narose after IT chemotherapy, including back pain, headache, fever, vomiting, and asthenia. At least one of these occurred after\n30.70% of IT chemotherapy doses. Clinicians involved in the care of patients receiving IT chemotherapy should be aware of these\nfindings and consider treatment options lower rate of neurotoxicity such as high-dose systemic methotrexate....
Abstract: Cullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an\noncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis.\nWe observed that Cul4A was over expressed in non-small cell lung cancer (NSCLC) tissues and the\nover expression of Cul4A was associated with poor prognosis after surgical resection and it also\ndecreased the expression of the tumor suppressor protein annexin A10 (ANXA10). The knockdown\nof Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was\nassociated with the down regulation of ANXA10 in lung cancer cells. Further studies showed that\nthe knockdown of Cul4A inhibited the invasion and metastasis of lung cancer cells, which was\nreversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited\nlung tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the\ndegradation of ANXA10 through its interaction with ANXA10 and ubiquitination in lung cancer\ncells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays\nimportant roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor\nsuppressor....
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