Apoptosis is a cellular suicide program that plays a critical role in development and human diseases, including cancer. Cancer cells evade apoptosis, thereby enabling excessive proliferation, ...survival under hypoxic conditions, and acquired resistance to therapeutic agents. Among various mechanisms that contribute to the evasion of apoptosis in cancer, metabolism is emerging as one of the key factors. Cellular metabolites can regulate functions of pro- and antiapoptotic proteins. In turn, p53, a regulator of apoptosis, also controls metabolism by limiting glycolysis and facilitating mitochondrial respiration. Consequently, with dysregulated metabolism and p53 inactivation, cancer cells are well-equipped to disable the apoptotic machinery. In this article, we review how cellular apoptosis is regulated and how metabolism can influence the signaling pathways leading to apoptosis, especially focusing on how glucose and lipid metabolism are altered in cancer cells and how these alterations can impact the apoptotic pathways.
Differentiating recurrence from benign posttreatment changes has clinical importance in the imaging follow-up of head and neck cancer. This study aimed to investigate the utility of normalized ...dynamic contrast-enhanced MR imaging and ADC for their differentiation.
This study included 51 patients with a history of head and neck cancer who underwent follow-up dynamic contrast-enhanced MR imaging with DWI-ADC, of whom 25 had recurrences and 26 had benign posttreatment changes. Quantitative and semiquantitative dynamic contrast-enhanced MR imaging parameters and ADC of the ROI and reference region were analyzed. Normalized dynamic contrast-enhanced MR imaging parameters and normalized DWI-ADC parameters were calculated by dividing the ROI by the reference region.
Normalized plasma volume, volume transfer constant between extravascular extracellular space and blood plasma per minute (
), area under the curve, and wash-in were significantly higher in patients with recurrence than in those with benign posttreatment change (
= .003 to <.001). The normalized mean ADC was significantly lower in patients with recurrence than in those with benign posttreatment change (
< .001). The area under the receiver operating characteristic curve of the combination of normalized dynamic contrast-enhanced MR imaging parameters with significance (normalized plasma volume, normalized extravascular extracellular space volume per unit tissue volume, normalized
, normalized area under the curve, and normalized wash-in) and normalized mean ADC was 0.97 (95% CI, 0.93-1).
Normalized dynamic contrast-enhanced MR imaging parameters, normalized mean ADC, and their combination were effective in differentiating recurrence and benign posttreatment changes in head and neck cancer.
The skull base osteomyelitis sometimes can be difficult to distinguish from nasopharyngeal cancer. This study aimed to investigate the differences between skull base osteomyelitis and nasopharyngeal ...cancer using dynamic contrast-enhanced MR imaging and normalized ADC values.
This study included 8 and 12 patients with skull base osteomyelitis and nasopharyngeal cancer, respectively, who underwent dynamic contrast-enhanced MR imaging and DWI before primary treatment. Quantitative dynamic contrast-enhanced MR imaging parameters and ADC values of the ROIs were analyzed. Normalized ADC parameters were calculated by dividing the ROIs of the lesion by that of the spinal cord.
The rate transfer constant between extravascular extracellular space and blood plasma per minute (Kep) was significantly lower in patients with skull base osteomyelitis than in those with nasopharyngeal cancer (median, 0.43 versus 0.57;
= .04). The optimal cutoff value of Kep was 0.48 (area under the curve, 0.78; 95% CI, 0.55-1). The normalized mean ADC was significantly higher in patients with skull base osteomyelitis than in those with nasopharyngeal cancer (median, 1.90 versus 0.87;
< .001). The cutoff value of normalized mean ADC was 1.55 (area under the curve, 0.96; 95% CI, 0.87-1). The area under the curve of the combination of dynamic contrast-enhanced MR imaging parameters (Kep and extravascular extracellular space volume per unit tissue volume) was 0.89 (95% CI, 0.73-1), and the area under the curve of the combination of dynamic contrast-enhanced MR imaging parameters and normalized mean ADC value was 0.98 (95% CI, 0.93-1).
Quantitative dynamic contrast-enhanced MR imaging parameters and normalized ADC values may be useful in differentiating skull base osteomyelitis and nasopharyngeal cancer. The combination of dynamic contrast-enhanced MR imaging parameters and normalized ADC values outperformed each measure in isolation.
Previous studies reported that the ADC values of recurrent head and neck cancer lesions are lower than those of posttreatment changes, however, the utility of ADC to differentiate them has not been ...definitively summarized and established.
Our aim was to evaluate the diagnostic benefit of ADC calculated from diffusion-weighted imaging in differentiating recurrent lesions from posttreatment changes in head and neck cancer.
MEDLINE, Scopus, and EMBASE data bases were searched for studies.
The review identified 6 prospective studies with a total of 365 patients (402 lesions) who were eligible for the meta-analysis.
Forest plots were used to assess the mean difference in ADC values. Heterogeneity among the studies was evaluated using the Cochrane Q test and the I
statistic.
Among included studies, the overall mean of ADC values of recurrent lesions was 1.03 × 10
mm
/s and that of the posttreatment changes was 1.51 × 10
mm
/s. The ADC value of recurrence was significantly less than that of posttreatment changes in head and neck cancer (pooled mean difference: -0.45; 95% CI, -0.59-0.32,
< .0001) with heterogeneity among studies. The threshold of ADC values between recurrent lesions and posttreatment changes was suggested to be 1.10 × 10
mm
/s.
Given the heterogeneity of the data of the study, the conclusions should be interpreted with caution.
The ADC values in recurrent head and neck cancers are lower than those of posttreatment changes, and the threshold of ADC values between them was suggested.
Differentiation of skull base tumors, including chondrosarcomas, chordomas, and metastases, on conventional imaging remains a challenge. We aimed to test the utility of DWI and dynamic ...contrast-enhanced MR imaging for skull base tumors.
Fifty-nine patients with chondrosarcomas, chordomas, or metastases between January 2015 and October 2021 were included in this retrospective study. Pretreatment normalized mean ADC and dynamic contrast-enhanced MR imaging parameters were calculated. The Kruskal-Wallis H test for all tumor types and the Mann-Whitney
test for each pair of tumors were used.
Fifteen chondrosarcomas (9 men; median age, 62 years), 14 chordomas (6 men; median age, 47 years), and 30 metastases (11 men; median age, 61 years) were included in this study. Fractional plasma volume helped distinguish all 3 tumor types (
= .003, <.001, and <.001, respectively), whereas the normalized mean ADC was useful in distinguishing chondrosarcomas from chordomas and metastases (
< .001 and
< .001, respectively); fractional volume of extracellular space, in distinguishing chondrosarcomas from metastases (
= .02); and forward volume transfer constant, in distinguishing metastases from chondrosarcomas/chondroma (
= .002 and .002, respectively) using the Kruskal-Wallis H test. The diagnostic performances of fractional plasma volume for each pair of tumors showed areas under curve of 0.86-0.99 (95% CI, 0.70-1.0); the forward volume transfer constant differentiated metastases from chondrosarcomas/chordomas with areas under curve of 0.82 and 0.82 (95% CI, 0.67-0.98), respectively; and the normalized mean ADC distinguished chondrosarcomas from chordomas/metastases with areas under curve of 0.96 and 0.95 (95% CI, 0.88-1.0), respectively.
DWI and dynamic contrast-enhanced MR imaging sequences can be beneficial for differentiating the 3 common skull base tumors.
Behcet's disease Suzuki Kurokawa, M; Suzuki, N
Clinical and experimental medicine,
09/2004, Letnik:
4, Številka:
1
Journal Article
Recenzirano
Behcet's disease (BD) is a systemic disorder of recurrent acute inflammation, characterized by major symptoms of oral aphthous ulcers, uveitis, skin lesions and genital ulcers. Involvement of ...intestines, vessels, and central nervous system (CNS) sometimes leads to a poor prognosis. Patients with BD are known to distribute along the ancient Silk Road. The incidence is relatively higher from eastern Asia to the Mediterranean area as roughly 1-10 patients in 10,000 people, whereas only 1-2 patients in 1,000,000 people in UK and North America. Although etiology of the disease is still unknown, high prevalence of HLA-B51, increased expression of heat shock protein 60 and Th1 dominant immune responses in the patients are considered important in its pathogenesis. Non-infectious neutrophil activation and infection with Streptococcus sanguis and herpes simplex virus would also be associated. Because BD lacks any pathognomonic symptoms and laboratory findings, the diagnosis relies largely upon the criteria proposed by the International Study Group for Behcet's disease in 1990. In Japan, the diagnosis was also made according to the Japanese criteria revised in 1987. Recently, the Behcet's Disease Research Committee of Japan again revised the Japanese criteria in 2003 to avoid overdiagnosis. The new Japanese criteria are introduced in this review. Differential diagnosis excluding Sweet's disease, pemphigus, erythema nodosum and Crohn's disease is important, and positive laboratory data for pathergy test, prick test for dead Streptococci and HLA-B51 are emphasized to make appropriate diagnosis in these criteria. Pathological findings of the disease-affected site such as erythematous nodosum is also stressed. Treatment for the disease has been chosen according to the clinical symptoms. Non-steroidal anti-inflammatory drugs, immunosuppressants, corticosteroids and colchicine are basically introduced. Recently, effects of interferon-alpha/beta, anti-tumor necrosis factor antibody and thalidomide are encouraging, specifically in treatment for the cases with poor prognosis including eye, intestine, vessel and CNS involvement. Low dose weekly administration of methotraxate looks effective for the cases with CNS involvement. Further studies for elucidation of the etiology, improvement of the diagnostic criteria and development of new therapy are needed to conquer the disease.
The transcription factor RUNX1 is a master regulator of hematopoiesis. Disruption of RUNX1 activity has been implicated in the development of hematopoietic neoplasms. Recent studies also highlight ...the importance of RUNX1 in solid tumors both as a tumor promoter and a suppressor. Given its central role in cancer development, RUNX1 is an excellent candidate for targeted therapy. A potential strategy to target RUNX1 is through modulation of its posttranslational modifications (PTMs). Numerous studies have shown that RUNX1 activity is regulated by PTMs, including phosphorylation, acetylation, methylation and ubiquitination. These PTMs regulate RUNX1 activity either positively or negatively by altering RUNX1-mediated transcription, promoting protein degradation and affecting protein interactions. In this review, we first summarize the available data on the context- and dosage-dependent roles of RUNX1 in various types of neoplasms. We then provide a comprehensive overview of RUNX1 PTMs from biochemical and biologic perspectives. Finally, we discuss how aberrant PTMs of RUNX1 might contribute to tumorigenesis and also strategies to develop anticancer therapies targeting RUNX1 PTMs.
Hypophysitis is one of the well-known adverse effects of immune checkpoint inhibitors. Immune checkpoint inhibitor-induced hypophysitis frequently causes irreversible hypopituitarism, which requires ...long-term hormone replacement. Despite the high frequency and clinical significance, characteristic MR imaging findings of immune checkpoint inhibitor-induced hypophysitis have not been established. In the present study, we aimed to review and extract the MR imaging features of immune checkpoint inhibitor-induced hypophysitis.
This retrospective international multicenter study comprised 20 patients with melanoma who were being treated with immune checkpoint inhibitors and clinically diagnosed with immune checkpoint inhibitor-induced hypophysitis. Three radiologists evaluated the following MR imaging findings: enlargement of the pituitary gland and stalk; homogeneity of enhancement of the pituitary gland; presence/absence of a well-defined poorly enhanced area and, if present, its location, shape, and signal intensity in T2WI; and enhancement pattern in contrast-enhanced dynamic MR imaging. Clinical symptoms and hormone levels were also recorded.
Enlargement of the pituitary gland and stalk was observed in 12 and 20 patients, respectively. Nineteen patients showed poorly enhanced lesions (geographic hypoenhancing lesions) in the anterior lobe, and 11 of these lesions showed hypointensity on T2WI. Thyrotropin deficiency and corticotropin deficiency were observed in 19/20 and 12/17 patients, respectively, which persisted in 12/19 and 10/12 patients, respectively, throughout the study period.
Pituitary geographic hypoenhancing lesions in the anterior lobe of the pituitary gland are characteristic and frequent MR imaging findings of immune checkpoint inhibitor-induced hypophysitis. They reflect fibrosis and are useful in distinguishing immune checkpoint inhibitor-induced hypophysitis from other types of hypophysitis/tumors.
Background: Patients with natural killer (NK) cell neoplasms, aggressive NK cell leukemia (ANKL) and extranodal NK cell lymphoma, nasal type (ENKL), have poor outcome. Both diseases show a spectrum ...and the boundary of them remains unclear. The purpose of this study is to draw a prognostic model of total NK cell neoplasms.
Patients and methods: We retrospectively analyzed 172 patients (22 with ANKL and 150 with ENKL). The ENKLs consisted of 123 nasal and 27 extranasal (16 cutaneous, 9 hepatosplenic, 1 intestinal and 1 nodal) lymphomas.
Results: Complete remission rate for ENKL was 73% in stage I, but 15% in stage IV, which was consistent with that for ANKL (18%). The prognosis of ENKL was better than that of ANKL (median survival 10 versus 1.9 months, P<0.0001) but was comparable when restricted to stage IV cases (4.0 months, P=0.16). Multivariate analysis showed that four factors (non-nasal type, stage, performance status and numbers of extranodal involvement) were significant prognostic factors. Using these four variables, an NK prognostic index was successfully constructed. Four-year overall survival of patients with zero, one, two and three or four adverse factors were 55%, 33%, 15% and 6%, respectively.
Conclusion: The current prognostic model successfully stratified patients with NK cell neoplasms with different outcomes.
The mean ADC value of the lower Gaussian curve (ADC
) derived from the bi-Gaussian curve-fitting histogram analysis has been reported as a predictive/prognostic imaging biomarker in patients with ...recurrent glioblastoma treated with bevacizumab; however, its systematic summary has been lacking.
We applied a systematic review and meta-analysis to investigate the predictive/prognostic performance of ADC
in patients with recurrent glioblastoma treated with bevacizumab.
We performed a literature search using PubMed, Scopus, and EMBASE.
A total of 1344 abstracts were screened, of which 83 articles were considered potentially relevant. Data were finally extracted from 6 studies including 578 patients.
Forest plots were generated to illustrate the hazard ratios of overall survival and progression-free survival. The heterogeneity across the studies was assessed using the Cochrane
test and I
values.
The pooled hazard ratios for overall survival and progression-free survival in patients with an ADC
lower than the cutoff values were 1.89 (95% CI, 1.53-2.31) and 1.98 (95% CI, 1.54-2.55) with low heterogeneity among the studies. Subgroup analysis of the bevacizumab-free cohort showed a pooled hazard ratio for overall survival of 1.20 (95% CI, 1.08-1.34) with low heterogeneity.
The conclusions are limited by the difference in the definition of recurrence among the included studies.
This systematic review with meta-analysis supports the prognostic value of ADC
in patients with recurrent glioblastoma treated with bevacizumab, with a low ADC
demonstrating decreased overall survival and progression-free survival. On the other hand, the predictive role of ADC
for bevacizumab treatment was not confirmed.
PDF
