Nuclei isolation from surgically resected human hippocampus.
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ABSTRACT:
SUBMITTER: Ayhan F
PROVIDER: S-EPMC8455478 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionDespite apparently complete surgical resection, approximately half of resected early-stage lung cancer patients relapse and die of their disease. Adjuvant chemotherapy reduces this risk by only 5% to 8%. Thus, there is a need for better identifying who benefits from adjuvant therapy, the drivers of relapse, and novel targets in this setting.MethodsRNA sequencing and liquid chromatography/liquid chromatography-mass spectrometry proteomics data were generated from 51 surgically resected non-small cell lung tumors with known recurrence status.ResultsWe present a rationale and framework for the incorporation of high-content RNA and protein measurements into integrative biomarkers and show the potential of this approach for predicting risk of recurrence in a group of lung adenocarcinomas. In addition, we characterize the relationship between mRNA and protein measurements in lung adenocarcinoma and show that it is outcome specific.ConclusionsOur results suggest that mRNA and protein data possess independent biological and clinical importance, which can be leveraged to create higher-powered expression biomarkers.
| S-EPMC7135954 | biostudies-literature
Project description:Few reports have investigated prognosis of canine gastrointestinal stromal tumor (GIST) cases treated by surgical resection alone. In the present study, we investigated the overall survival (OS) and prognostic factors for dogs with GIST treated by surgical complete resection alone. Fifty-three dogs were included, and the median OS was 18 months. Multivariate analysis showed that primary tumors in small intestine (P=0.04) is significantly associated with shorter OS, and median OS of the cases with cecum lesion and those with small intestine lesion was 22 and 6 months, respectively. The present study suggested primary tumor site was a novel prognostic factor for dogs with GIST treated by surgical complete resection alone.
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Project description:BACKGROUND:Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis. METHODS:IMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the effect of IMMT expression on survival. RESULTS:High-IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06-3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation. CONCLUSION:Here, we first demonstrated that high-IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.
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Project description:Glioblastoma is a heterogeneous glial cell malignancy with extremely high morbidity and mortality. Current treatment is limited and provide minimal therapeutic efficacy. Previous studies were reliant on cell lines that do not accurately reflect the heterogeneity of the glioma microenvironment. Developing reliable models of human glioblastoma is therefore essential. Direct culture of human brain tumours is often difficult and there is a limited number of protocols available. Hence, we have developed an effective method for the primary culture of human glioblastoma samples obtained during surgical resection. Culturing tumour tissue direct from human brain is advantageous in that cultures (1) more closely resemble true human disease, relative to the use of cell lines; (2) comprise a range of cellular components present in the natural tumour microenvironment; and (3) are free of added antibodies and reagents. Additionally, primary glioblastoma cultures are valuable in studies examining the effects of anti-cancer pharmaceuticals and therapeutic agents, and can be further used in live cell imaging, immunocytochemistry, flow cytometry and immunoassay experiments. Via this protocol, cells are maintained in supplemented medium at 37 °C (5% CO2) and are expected to achieve sufficient confluency within 7 days of initial culture.
| S-EPMC7189671 | biostudies-literature
Project description:Background:It has not been determined if adjuvant chemotherapy would be helpful for completely resected early-stage lung adenocarcinoma even with unfavorable genetic markers. As the positive anaplastic lymphoma kinase (ALK) rearrangement is associated with aggressive clinical feature in lung adenocarcinoma, we evaluated the treatment outcomes of completely resected stage IA lung adenocarcinoma according to initial ALK status. Methods:This is a retrospective cohort study including 309 patients with surgically resected stage IA lung adenocarcinoma from February 2010 to December 2013. Patients were screened for ALK rearrangement using immunohistochemistry. A positive ALK status was defined as an immunohistochemistry score of 2+ or more. Both disease-free survival (DFS) and the initial recurrence pattern were analyzed according to ALK status. Results:Twenty-three (7.4%) patients had ALK-positive adenocarcinoma. During the median follow-up of 35.8 months, recurrence developed in 34 (11.0%) patients. The patients with ALK-positive tumor had significantly lower 5-year DFS rate (62.4%) compared to those with ALK-negative tumor (86.5%; P=0.038). The multivariable analysis showed that ALK rearrangement was associated with a higher risk of disease recurrence (adjusted hazard ratio =2.64; 95% confidence interval, 1.08-6.44). In addition, patient with ALK-positive tumor showed more frequent recurrence in regional lymph nodes compared with those with ALK-negative tumor (83.3% vs. 28.6%; P=0.031). Conclusions:In patients with completely resected stage IA lung adenocarcinoma, ALK rearrangement was associated with unfavorable DFS and more frequent regional lymph node metastasis. Therefore, careful surveillance for recurrence should be performed in this subset of patients.
| S-EPMC6051845 | biostudies-literature
Project description:BACKGROUND:The role of postoperative radiotherapy (PORT) in patients with clinical stage III-N2 (cIII-N2) non-small cell lung cancer (NSCLC) treated with induction chemotherapy and surgical resection with persistent ypN2 disease is not well established. METHODS:We retrospectively reviewed a prospectively maintained database for patients with cIII-N2 NSCLC who underwent induction chemotherapy followed by resection (2004-2016). Exclusion criteria included induction radiotherapy, non-biopsy-confirmed cN2 disease, incomplete resection, ypN0/1, and nonanatomic resection. The primary outcome was locoregional recurrence (LR); secondary outcomes were disease-free survival (DFS), lung cancer-specific death (LCSD), and overall survival (OS). Associations between variables and outcomes were assessed using Fine and Gray competing risk regression for LR/LCSD and Cox proportional hazard models for survival. RESULTS:Of the 501 patients identified with cIII-N2 disease, 99 met the inclusion criteria. Median follow-up was 25 months (range, 3-137 months). Sixty-nine patients (70%) received PORT. Sixty (61%) developed a recurrence: 3 (5%) with an initial isolated LR and 57 (95%) with an initial distant recurrence. On multivariable analysis, PORT was not associated with LR (HR, 0.51 [95% CI, 0.22-1.21], p = 0.13). PORT was also not associated with DFS (p = 0.6) or LCSD (p = 0.1). PORT was associated with improved 3-year OS (55% [95% CI, 42%-71%]) versus the no-PORT group (50% [95% CI, 34%-74%]) (p = 0.04). CONCLUSIONS:PORT is not independently associated with decreased LR or improved DFS/LCSD in this patient population. Given that the predominant failure pattern was distant recurrence, future clinical trials should focus on adjuvant systemic therapies, which may decrease distant recurrences in ypN2 patients.
| S-EPMC6136648 | biostudies-literature
Project description:This article presents supplementary data for the research article by Yotsukura et al. entitled "Prognostic impact of cancer-associated active fibroblasts and invasive architectural patterns on early-stage lung adenocarcinoma" [1], which presented the postoperative prognosis for early-stage lung adenocarcinoma categorized according to histological findings. We included data of 1,032 resected cases of lung adenocarcinoma, which consisted of pathological stage IA invasive cancer and adenocarcinoma in situ resected at National Cancer Center Hospital, Tokyo, Japan, between 2007 and 2012. A pathological review was performed to assess total tumor size, size of invasion, histological subtype, lymphovascular invasion, and presence of cancer-associated active fibroblast (CAF). Tumor recurrence and overall survival were retrospectively recorded. Of the included cases, 166 (16.1%), and 866 (83.9%) were adenocarcinoma in situ and pathological stage IA, respectively. Pathological stage IA adenocarcinoma was further classified based on the histologial subtype and the presence of CAF. This data set may be useful for analyzing the postoperative prognosis of early-stage lung adenocarcinoma, in combination with detailed pathological findings including size of invasion, histological subtype, and presence of CAF.
| S-EPMC7287229 | biostudies-literature
Project description:Angiosarcoma is a rare type of soft-tissue sarcoma arising from endothelial cells. It is considered 'high-grade' by definition, reflecting its aggressive behavior. We sought to investigate the role of surgery in cardiac angiosarcoma, identify late mortality predictors, and identify interactions with other modalities in its treatment using a national dataset. The 2004-2017 National Cancer Database was reviewed for patients with primary cardiac angiosarcoma. Late mortality predictors were evaluated with Kaplan-Meier curves and Cox regression analysis. Surgery in primary cardiac angiosarcoma was performed in 130 patients (median age 50.5 years; female sex 36.9%). The median follow up was 72.02 months, with a median overall survival (OS) of 14.32 months. In patients treated with surgery in combination with other modalities compared with those treated with surgery alone, median OSs were 17.28 and 2.88 months, respectively (log-rank = 0.018). Older patients (age > 57 years) experienced lower OS compared to those with an age < 57 (log-rank = 0.012). This may be partially explained by the difference in treatment strategies among age groups: those with increasing age, less surgery (p = 0.037), and less chemotherapy (p < 0.001) were chosen. With multivariable Cox regression analysis, age and race other than white or black were identified to be significant independent predictors of late mortality. Cardiac angiosarcoma has poor overall survival, and our findings should further encourage the use of surgery in combination with other therapeutic modalities in treating such an aggressive disease whenever possible.
| S-EPMC10744152 | biostudies-literature
Project description:ImportanceHuman papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a distinct form of head and neck squamous cell carcinoma (HNSCC) with its own American Joint Committee on Cancer staging system. However, pathologic risk stratification for HPV+ OPSCC largely remains based on the experience with HPV-unassociated HNSCC.ObjectiveTo compare the survival discrimination of traditional pathologic risk stratification for both HPV+ OPSCC and HPV-unassociated HNSCC and derive a novel pathologic risk stratification system for HPV+ OPSCC with improved survival discrimination.Design, setting, and participantsIn this retrospective cohort study, we used the National Cancer Database to identify 15 324 patients diagnosed with nonmetastatic HNSCC between January 1, 2010, and December 31, 2013, who were treated with upfront surgery and neck dissection. We compared traditional pathologic risk stratification for HPV+ OPSCC and HPV-unassociated HNSCC and then derived a novel pathologic risk stratification system. Analyses were performed from July 1, 2018, to January 31, 2019.ExposuresDefinitive primary surgical resection and neck dissection.Main outcomes and measuresSurvival discrimination of pathologic risk stratification systems measured with concordance indices.ResultsThis retrospective cohort study included 15 324 patients (10 779 men and 4545 women; mean [SD] age, 59.9 [11.8] years) with surgically treated nonmetastatic HNSCC. Separation of survival curves for HPV-unassociated HNSCC using traditional pathologic risk stratification (5-year overall survival for the low-, intermediate-, and high-risk groups) were 76.2%, 54.5%, and 40.9%, respectively. Separation curves for HPV+ OPSCC were 93.2%, 88.9%, and 83.7%, respectively. Human papillomavirus-unassociated HNSCC had a concordance index of 0.68, whereas HPV+ OPSCC had a concordance index of 0.58. A novel risk stratification system for HPV+ OPSCC that more closely fits actual survival rates for HPV+ OPSCC was derived. The system incorporated the composite number of pathologic adverse features. This composite risk stratification system was associated with an improved concordance index of 0.67 for HPV+ OPSCC. Adjuvant treatment with radiation was not associated with improved survival for patients categorized as low risk according to the new risk stratification system, but this treatment was associated with improved survival for patients in the intermediate- and high-risk groups.Conclusions and relevanceTraditional pathologic risk stratification shows poor survival discrimination for HPV+ OPSCC and classifies many patients with an excellent prognosis as high risk. We derived a novel composite pathologic risk stratification system for HPV+ OPSCC that may be associated with improved survival discrimination.
| S-EPMC6495356 | biostudies-literature
Project description:The aim of this study was to evaluate the clinicopathological and prognostic relevance of PIK3CA mutations in Chinese patients with surgically resected cervical cancer. PIK3CA mutations were screened in 771 cervical cancer specimens using reverse transcription polymerase chain reaction and Sanger sequencing. In total, 13.6% (105 of 771) of patients harbored non-synonymous PIK3CA mutations. Patients harboring PIK3CA mutations were older than patients with wild-type PIK3CA (mean age: 50.7 years vs. 47.0 years, P?<?0.01). PIK3CA mutations were more commonly observed in postmenopausal patients than in premenopausal patients (19.6% vs. 10.2%, P?<?0.01). PIK3CA mutations were more common in squamous cell carcinomas than in non-squamous cell tumors (15.3% vs 7.3%, of P?<?0.01). The 3-year relapse-free survival was 90.2% for PIK3CA mutant patients and 80.9% for PIK3CA wild-type patients (P?=?0.03). PIK3CA mutation was confirmed as an independent predictor for better treatment outcome in the multivariate analyses (HR?=?0.54, 95% CI: 0.29-0.99, P?=?0.048). PIK3CA mutations were significantly associated with less distant metastases (mutant-type: 8/105, wild-type: 98/666, p?=?0.048). Thus, patients with mutant PIK3CA had distinct characteristics in age, menopausal status, and histological subtype and have better treatment outcome and less distant metastasis after surgery-based multimodal therapy.
| S-EPMC4566086 | biostudies-other