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At least 19 recordsLinked to original sources
PubMed2026

The clinical landscape of POLE-mutant colorectal cancer: a retrospective analysis of real-world outcome.

BACKGROUND: Pathogenic mutations in the POLE gene disrupt its proofreading function during DNA replication, causing an accumulation of erroneous nucleotide incorporations. This defect leads to a significantly elevated tumor mutation burden (TMB) and increased generation of tumor neoantigens. These molecular characteristics suggest a potential association between POLE-mutant tumors and distinct prognostic outcomes in colorectal cancer (CRC); however, clinical evidence supporting this correlation remains limited. METHODS: We retrospectively collected a cohort of CRC patients harboring pathogenic POLE mutations. Comparative analyses were performed between POLE-mutant and POLE wild-type CRCs regarding their clinical characteristics, prognostic outcomes, and genomic profiles. Additionally, we evaluated the response to immunotherapy in metastatic POLE-mutant CRC cases. RESULTS: Among 35,108 CRC patients, pathogenic POLE mutations were identified in 261 individuals, accounting for 0.74% of the cohort. The median age at diagnosis for POLE-mutant patients was 48 years, with a male predominance (74.4%) and a substantial proportion (50.4%) of tumors localized in the right-sided colon. All patients with pathogenic POLE mutations exhibited hypermutated phenotypes, characterized by a median TMB of 235.26 mutations per megabase (range: 71.20-719.00 mutations/Mb). In stage II CRC, POLE mutations were significantly associated with a reduced risk of recurrence (hazard ratio [HR] 0.344, 95% confidence interval [CI] 0.157-0.754, p = 0.008) when compared to POLE wild-type, microsatellite stable CRC patients. However, this association was not evident in stage III patients (HR 1.004, 95% CI 0.490-2.057, p = 0.992). Importantly, the incorporation of immune checkpoint inhibitors in first-line treatment regimens significantly improved progression-free survival (HR = 0.247, 95% CI 0.117-0.552, p = 0.0002) and overall survival (HR = 0.317, 95% CI 0.103-1.143, p = 0.0832) in metastatic CRC patients with pathogenic POLE mutations. CONCLUSIONS: Pathogenic POLE-mutant CRC constitutes a relatively rare, yet clinically important, subtype. These cancers exhibit distinct clinicopathological and genomic features. Our results indicate that mutations in the POLE gene may serve as a valuable prognostic marker and a potential indicator of benefit to immunotherapy in CRC, offering promising avenues for personalized treatment strategies.

Humans↗
PubMed1975

[Frequency of genes and blood groups of the systems, ABO, MN, Rh and P among the Belerussians and Poles of the Grodno region].

A distribution of the gene frequencies and blood groups of the ABO, Rh, NM and P system in the poles and the byelorussians inthe Grodno region is investigated. The following frequencies of genes in the byelorussians were revealed: r(O)--0,6210; P(A)--0,2451; Q(B)--0,1339; D--0,6093; D-9,3907; M-0,6063; N-0,3937; P(+)-0,4971; P(--)--0,5029; and in poles: r(O)--0,6284; p(A)--0,2353; q(B)--0,1363; D - 0,6065; d - 0,3935; M - 0,6093; N- 0,0397; P(+) -0,4966; P(-) -0,5034. No statistically reliable differences were revealed in frequencies of the alleles an d phenotypes of the investigated systems in the poles and byelorussians. By comparison of the same isoantigen systems of the byelorussians in the Grodno region with the common population of the byelorussians in the BSSR it was found that statistically significant differences do not exist. The comparison of the poles in the Grodno region withthe poles in the Polish People's Republic showed a statistically reliable difference of their genofunds in terms of the gene frequencies: r(O) , p(A), D, d, P(+), P(-). This confirms the hypothesis about an indigenous origin of the poles in the Grondno region.

ABO Blood-Group System↗
PubMed1975

[Frequency of genes and blood groups of the systems ABO, MN, Rh and P of Belorussians and Poles in the Grodno region].

A distribution of the gene frequencies and blood groups of the ABO, Rh, NM and P system in the poles and the byelorussians in the Grodno region is investigated. The following frequencies of genes in the byelorussians were revealed: r(0)-0,6210; p(A)-0.2451; q(B)-0,1339; D-0,6093; d-0,3907; M-06063; N-0,3937; P(+)-0,4971; P(-)-0,5029; and in the poles: r(O)-0,6284; p(A)-0,2353; q(B)-0,1363; D-0,6065; d-0,3935; M-0,6093; N-0,397; P(+)-0,4966; P(-)-0,5034. No statistically reliable differences were revealed in frequencies of the alleles and phenotypes of the investigated systems in the poles and byelorussians. By comparison of the same isoantigen systems of the byelorussians in the Grodno region with common population of the byelorussians in the BSSR it was found that statistically significant differences do not exist. The comparison of the poles in the Grodno region with the poles in the Polish People's Republic showed a statistically reliable difference of their genofunds in terms of the gene frequencies: r(O), p(A), D, d, P(+), P(-). This confirms the hypothesis about an indigenous origin of the poles in the Grodno region.

ABO Blood-Group System↗
PubMed1975

[Frequency of genes and blood groups of the ABO, MN, Rh and P systems among Belorussians and Poles in the Grodno region].

A distribution of the gene frequencies and blood groups of the ABO, Rh, NM and P system in the poles and the byelorussians in the Grodno region is investigated. The following frequencies of genes in the byelorussians were revealed: r(0)-0,6210; p(A)--0.2451; q(B)--0,1339; D--0,6093; d--0,3907; M--0,6063; N--0,3937; P(+)-- 0,4971; P(--)--0,5029; and in the poles: r(0)--0,6284; p(A)--0,2353; q(B)--0,1363; D--0,6065; d - 0,3935; M - 0,6093; N - 0,0397; P(+) - 0,4966; P(-) - 0,5034. No statistically reliable differences were revealed in frequencies of the alleles and phenotypes of the investigated systems in the poles and byelorussians. By comparison of the same isoantigen systems of the byelorussians in the Grodno region with the common population of the byelorussians in the BSSR it was found that statistically significant differences do not exist. The comparison of the poles in the Grodno region with the poles in the Polish People's Republic showed a statistically reliable difference of their genofunds in terms of the gene frequencies: r(0), p(A), D, d, P(+), P(-). This confirms the hypothesis about an indigenous origin of the poles in the Grodno region.

ABO Blood-Group System↗
PubMed2026

Deficiency in POLE Exonuclease Causes Synthetic Lethality in Highly Aneuploid Cancer Cells.

UNLABELLED: Aneuploidy is a hallmark of cancer and is associated with drug resistance and poor clinical outcomes across diverse cancer types. However, no therapies have been clinically established to target highly aneuploid tumors. By analyzing nearly half a million tumor samples subjected to comprehensive genomic profiling, we identified a striking mutual exclusivity between POLE exonuclease domain mutations and high aneuploidy burden. This observation was independently validated using data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). Probabilistic modeling revealed that the elevated quantity and unique spectrum of mutations induced by POLE exonuclease deficiency increase the likelihood of inactivating essential genes on chromosome arms harboring losses, leading to a synthetic lethal phenotype in highly aneuploid cells. Functional experiments demonstrated that POLE exonuclease activity is essential for the viability of highly aneuploid cancer cell lines but dispensable in diploid cells. These findings suggest that selective inhibition of POLE exonuclease activity may represent a promising therapeutic strategy for targeting highly aneuploid tumors. SIGNIFICANCE: An integrated approach using large-scale genomic analyses, probabilistic modeling and functional validation identified POLE exonuclease as a potential synthetic lethal target to overcome cancer aneuploidy.

Humans↗
PubMed2026

Role of External Vibratory Lithoclast (Lithecbole) in Improving Lower Pole Stone Clearance After Extracorporeal Shock Wave Lithotripsy (ESWL).

<b>Background and Objective:</b> Extracorporeal shock wave lithotripsy (ESWL) is a widely used non-invasive treatment for renal stones. However, its effectiveness in clearing stones located in the lower pole of the kidney is often limited due to the anatomical challenges that impede the spontaneous passage of fragmented stones. This study evaluate the efficacy and safety of External Physical Vibration Lithecbole (EPVL) when used as an adjunctive therapy following ESWL in patients with lower pole renal stones, with a focus on improving stone clearance rates. <b>Materials and Methods:</b> This prospective interventional study was conducted at Al Yarmouk Teaching Hospital over two years and included 100 patients with 10-15 mm lower pole renal stones. Patients were randomized into two groups: The ESWL alone and ESWL plus EPVL. All patients received two ESWL sessions (3000 shocks/session). The treatment group additionally received EPVL therapy using a flank-applied vibration device. Follow-up was performed using ultrasound and KUB radiography. Statistical analysis was conducted using appropriate tests with significance set at p<0.05. <b>Results:</b> Baseline characteristics, including age, gender, weight, stone size and location, were statistically comparable between groups. The mean stone size was 12.4&#xb1;1.7 mm. A significantly higher stone-free rate was observed in the ESWL+EPVL group compared to the ESWL-only group (66% vs. 48%, p = 0.027). Although the residual stone size showed a numerical difference favoring EPVL, it was not statistically significant (p = 0.11). Complication rates were low, mild and similar in both groups (p = 0.3). Logistic regression analysis revealed that smaller stone size (p<0.001) and lower patient weight (p = 0.030) were significantly associated with successful stone clearance. Subgroup analysis further confirmed that patients with stones <11 mm or a weight <70 kg had the highest stone-free rates. <b>Conclusion:</b> In this initial evaluation, EPVL demonstrated a safe and effective adjunct to ESWL in enhancing stone clearance for lower-pole renal stones. Its application was associated with improved treatment outcomes without increasing complication rates. Further studies with extended EPVL sessions and longer follow-up are warranted.

Humans↗
PubMed1979

Posterior pole neovascularization in a patient with hemoglobin SC disease.

A 33-year-old black woman with hemoglobin SC disease and a history of photocoagulation for peripherally located retinal neovascularization had a neovascular frond at the temporal border of her right macula. Multiple zones of black sunburst hyperpigmentation were located nearby. Fluorescein angiography showed that the lesions were closely related to an extensive zone of avascular retina in the posterior pole. The perifoveal vasculature was uninvolved, and the patient was unaware of any visual deficit. Although sickle cell maculopathy is a well-recognized entity, there have been no published reports, to the best of our knowledge, of posterior pole neovascularization in patients with sickle cell hemoglobinopathy. The fluorescein angiographic findings in our case provide further support for the hypothesis that retinal hypoxia is an important stimulus for retinal neovascularization.

Adult↗
PubMed1977

[Partial disorganization of the anaphasic segregation of chromosomes in plant cells: combined actions of griseofulvin, producer of pluripolar anaphases and 2 ipecac alkaloids, producers of floating pole anaphases].

Anaphasis may be slightly checked by various treatments which however result in a normal chromosomic separation. Griseofulvin exerts a direct though partial influence on the mitotic apparatus, which entails "pluripolar anaphasis"; on the other hand Ipecac alkaloïds act indirectly and produce "floating poles anaphases". Treatments combining griseofulvin with cepheline or tubulosine show that there is never any synergy between the two processes. These results support our hypothesis that floating poles anaphases are not a sign of slight C-mitotic action but only come from a lag between the appearance/disappearance of microtubules and that of chromosomes during anaphasis.

Anaphase↗
PubMedDate not supplied

[Behavioral reactions in simians after ablation of the pole of the frontal cortex].

In 4 baboons and 3 macaques ablation of the frontal pole (area 10) as compared to other areas of the frontal cortex did not impair previously elaborated instrumental reflexes of different complexity and did not interfere with the elaboration of new ones. An increase in stability, speed, accuracy and intensity of conditioned reflexes was noted. The ablation did not result in motor or vegetative disturbances. In the general behaviour inhibitory elements disappeared along with an enhancement in motor goal-directed activity. It is suggested that frontal poles do not participate in closing-function but control conditioned reflexes and complex behaviour by means of inhibitory influences.

Animals↗
PubMed2026

Subtle cortical thinning in the temporal pole in middle-aged APOE-&#x3b5;4 and PICALM (rs3851179) AA/AG carriers without dementia.

The symptoms of Alzheimer's disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal lobe. However, the influence of genetic risk on cortical thickness prior to dementia onset, remains unclear. This study aimed to explore the relationship between AD genetic risk (related to APOE and PICALM genes) and cortical thickness in selected regions of interest (ROIs) in middle-aged individuals without dementia. Sixty-nine (N&#x202f;=&#x202f;69) participants (34 females, 35 males; age: 55.45&#x202f;&#xb1;&#x202f;3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their genetic AD risk: A+&#x202f;P+&#x202f;(APOE/PICALM risk variants), A+P- (APOE risk variant, PICALM neutral variants), and the N group (APOE/PICALM neutral alleles). Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred to as "the cortical signature of AD" in previous studies. The A+P- group had a thinner right temporal pole cortex than non-carriers after controlling for sex, age, and Raven's Progressive Matrices scores. Although this finding did not survive FDR correction across the 10 tested regions, it is consistent with our hypotheses and prior literature. No other differences in cortical thickness were found in the analyzed regions of AD "signature". The observed effect was restricted to single-risk APOE carriers without PICALM risk alleles. Therefore, further research is needed to understand the genetic interplay between these two genes in conferring AD risk.

Humans↗
PubMedDate not supplied

[Transmission of the anterior chamber pressure to the center of the vitreous body and to the posterior pole of the eye of the miniature swine. Measurement of isovolumetric and direct pressure].

Experimental variations of the anterior chamber pressure (P.I.C.) are transmitted at about 300 ms to the middle of the vitreous. The response time to a sudden experimental increase in P.I.C. to the centre of the vitreous is variable and depends essentially on the control intra-ocular pressure: the more it is raised the shorter the response time. The pressure in the centre of the vitreous (P.I.V.) has a pulsatile character probably due to transmission of arterial pulsation. The higher the intra-ocular pressure the greater the amplitude of these pulsations. Recording of P.I.V. close to the surface of the retina show abrupt falls despite the fact that the P.I.C. and systemic arterial pressure remain stable. These results are discussed in relationship to autoregulation of the retinal circulation and the physiopathology of glaucoma.

Animals↗