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Clinical Toxicology (Philadelphia, Pa.) Jun 2010Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut... (Review)
Review
INTRODUCTION
Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome.
METHODS
We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included "colchicine" and "poisoning" or "overdose" or "toxicity" or "intoxication."
TOXICOKINETICS
Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. THERAPEUTIC AND TOXIC DOSES: The usual adult oral doses for FMF is 1.2-2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5-0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg.
DRUG INTERACTIONS
CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy.
MECHANISMS OF TOXICITY
Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi-organ dysfunction and failure. REPRODUCTIVE TOXICOLOGY AND LACTATION: Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation.
CLINICAL FEATURES
Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness.
DIAGNOSIS
History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia).
MANAGEMENT
Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available.
CONCLUSION
Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adult; Charcoal; Clarithromycin; Clinical Trials as Topic; Colchicine; Colony-Stimulating Factors; Drug Interactions; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Familial Mediterranean Fever; Female; Granulocyte Colony-Stimulating Factor; Humans; Male
PubMed: 20586571
DOI: 10.3109/15563650.2010.495348 -
Journal of the American Academy of... Dec 2015Animal-type melanoma is a rare subtype of melanoma with heavily pigmented dermal epithelioid and spindled melanocytes. Its classification as a subtype of melanoma versus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Animal-type melanoma is a rare subtype of melanoma with heavily pigmented dermal epithelioid and spindled melanocytes. Its classification as a subtype of melanoma versus a borderline melanocytic tumor is debated.
OBJECTIVES
Our primary objective was to characterize the demographics, clinical presentation, histopathology, management, and outcomes of patients with animal-type melanoma.
METHODS
We performed a systematic review and meta-analysis of the English-language literature on animal-type melanoma.
RESULTS
We identified 190 cases of animal-type melanoma. They occurred equally in men and women, with Caucasians (53.7%) most commonly affected. The median Breslow depth was 3.8 mm; ulceration was reported present in 15.8%; and dermal mitoses greater than or equal to 1/mm(2) was reported in 27.4%. The most common initial management was wide local excision with sentinel lymph node biopsy (55.7%). In all, 78 patients underwent sentinel lymph node biopsy with 41.0% positivity rate. A total of 32 patients underwent completion lymph node dissection with 34.4% positivity rate. Locoregional recurrence was reported in 15 patients, recurrence with distant metastases in 6 patients, and death in 5 patients.
LIMITATIONS
Data were obtained from small studies with limited follow-up. There is no universally accepted definition of animal-type melanoma.
CONCLUSION
Prospective studies with complete staging information and molecular profiling may allow further characterization of this tumor.
Topics: Biopsy, Needle; Female; Humans; Immunohistochemistry; Incidence; Male; Melanocytes; Melanoma; Prognosis; Prospective Studies; Rare Diseases; Risk Assessment; Skin Neoplasms
PubMed: 26412164
DOI: 10.1016/j.jaad.2015.08.016 -
Critical Reviews in Clinical Laboratory... Feb 2024KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as... (Review)
Review
KIF2C/MCAK a prognostic biomarker and its oncogenic potential in malignant progression, and prognosis of cancer patients: a systematic review and meta-analysis as biomarker.
KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as well as interphase. This systematic review briefly describes the important structural elements of KIF2C, its regulation by multiple molecular mechanisms, and its broad cellular functions. Furthermore, it systematically summarizes its oncogenic potential in malignant progression and performs a meta-analysis of its prognostic value in cancer patients. KIF2C was shown to be involved in multiple crucial cellular processes including cell migration and invasion, DNA repair, senescence induction and immune modulation, which are all known to be critical during the development of malignant tumors. Indeed, an increasing number of publications indicate that KIF2C is aberrantly expressed in multiple cancer entities. Consequently, we have highlighted its involvement in at least five hallmarks of cancer, namely: genome instability, resisting cell death, activating invasion and metastasis, avoiding immune destruction and cellular senescence. This was followed by a systematic search of KIF2C/MCAK's expression in various malignant tumor entities and its correlation with clinicopathologic features. Available data were pooled into multiple weighted meta-analyses for the correlation between KIF2C protein or gene expression and the overall survival in breast cancer, non-small cell lung cancer and hepatocellular carcinoma patients. Furthermore, high expression of KIF2C was correlated to disease-free survival of hepatocellular carcinoma. All meta-analyses showed poor prognosis for cancer patients with KIF2C expression, associated with a decreased overall survival and reduced disease-free survival, indicating KIF2C's oncogenic potential in malignant progression and as a prognostic marker. This work delineated the promising research perspective of KIF2C with modern and technologies to further decipher the function of KIF2C in malignant tumor development and progression. This might help to establish KIF2C as a biomarker for the diagnosis or evaluation of at least three cancer entities.
PubMed: 38344808
DOI: 10.1080/10408363.2024.2309933 -
Cells Jun 2021Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological...
Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress ("Traumatic Stress Disorder" or "Anxiety Disorder" or "depression") and telomere length ("cellular senescence", "oxidative stress" and "telomere") was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.
Topics: Humans; Mental Disorders; Mitochondria; Oxidative Stress; Telomere; Telomere Shortening
PubMed: 34200513
DOI: 10.3390/cells10061423 -
Acta Neurochirurgica Aug 2022Tumor-treating fields (TTF) is a novel cancer treatment that uses alternating electric fields to interfere with tumor cell mitosis. It has been approved by the U.S. food... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tumor-treating fields (TTF) is a novel cancer treatment that uses alternating electric fields to interfere with tumor cell mitosis. It has been approved by the U.S. food and drug administration for the treatment of recurrent glioblastoma (rGBM). We designed this meta-analysis to evaluate the efficacy and safety of TTF in the treatment of rGBM.
METHODS
The study was based on the PRISMA guideline. Systematic retrieval was performed in PubMed, Cochrane Library, and Embase databases. The outcomes were overall survival (OS) hazard ratio (HR), 1-year survival rate, and cutaneous toxicity.
RESULTS
These studies included a total of 1048 rGBM patients who received TTF treatment. The overall survival time between the TTF group and the control group was HR 0.75 ([95%CI 0.63 to 0.89]; P = 0.001). Pooled 1-year overall survival rate and incidence of cutaneous toxicity were 0.47 and 0.48, respectively. Data were insufficient to evaluate the effect of MGMT methylation status and tumor recurrence times on heterogeneity.
CONCLUSIONS
TTF therapy is effective for recurrent glioblastoma. However, most relevant trials should assess rGBM patient baseline characteristics such as age, KPS, MGMT methylation status, and number of tumor recurrence,. In addition, the risk of rashes caused by long-term wearing of devices should also be considered.
Topics: Brain Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local
PubMed: 35397674
DOI: 10.1007/s00701-022-05192-z -
Thyroid : Official Journal of the... Mar 2024The current edition of the World Health Organization (WHO) classification of endocrine tumors introduced grading for follicular cell-derived thyroid cancer. Tumors with... (Meta-Analysis)
Meta-Analysis
The current edition of the World Health Organization (WHO) classification of endocrine tumors introduced grading for follicular cell-derived thyroid cancer. Tumors with necrosis and/or high mitotic count but not fulfilling the Turin criteria for poorly differentiated carcinoma will be reclassified as differentiated high-grade thyroid carcinoma (DHGTC). However, the impact of this reclassification has not been evaluated. In this study, we performed a systematic review and meta-analysis to estimate the prevalence of this new entry across thyroid tumor subtypes. In this systematic review and meta-analysis, studies reporting data on necrosis and/or mitoses in well-differentiated thyroid carcinoma (WDTC) were used to estimate the prevalence of DHGTC. Heterogeneity and potential publication bias were also evaluated. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and quality assessment was performed using a modification of the Newcastle-Ottawa scale. The study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022378716). In clinically unselected patients, the prevalence of DHGTC in WDTC was 0.072 [95% confidence interval, CI, = 0.045-0.113]. The proportion of high-grade tumors greatly varied across growth patterns and subtypes. Overall, the prevalence of DHGTC was higher in follicular thyroid carcinoma (FTC; 0.146 [CI = 0.101-0.205]) than in papillary thyroid carcinoma (PTC; 0.059 [CI = 0.036-0.097]). Diffuse sclerosing, follicular, and classic subtype PTC had the lowest rates of high-grade features (i.e., 0.018 [CI = 0.004-0.084]; 0.036 [CI = 0.010-0.124]; and 0.042 [CI = 0.027-0.066], respectively), while a greater proportion of solid trabecular and histologically aggressive PTC could be reclassified as DHGTC (i.e., 0.154 [CI = 0.067-0.314] and 0.168 [CI = 0.108-0.252], respectively). Similar proportions were obtained for minimally and widely invasive FTC (i.e., 0.136 [CI = 0.058-0.287] and 0.152 [CI = 0.086-0.254], respectively). Finally, in a cohort of patients with poor prognosis (i.e., fatal cases, metastatic and radioiodine resistant tumors, cases with biochemical recurrence), the proportion of DHGTC was 0.287 [CI = 0.155-0.469]. Following the current WHO indications, some tumors will be reclassified as DHGTC. The proportion of tumors with high-grade features is relevant in FTC, solid trabecular, and histologically aggressive PTC subtypes. A remarkable enrichment in DHGTC among patients with poor prognosis confirms the negative impact of high-grade features on outcome.
Topics: Humans; Iodine Radioisotopes; Prevalence; Thyroid Neoplasms; Adenocarcinoma, Follicular; Necrosis
PubMed: 38115626
DOI: 10.1089/thy.2023.0350 -
Journal of Clinical Medicine Apr 2023Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and... (Review)
Review
Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and vascular abnormalities. We present a systematic review of the literature to provide clarity on chorangiocarcinoma entity and biology. A literature search was carried out in December 2022 using the keywords "Placental chorangiocarcinoma", "Chorangioma", "Placenta", and "Throphoblast proliferation". Articles published from 1988 to 2022 were obtained from Scopus, Google Scholar, and PUBMED. In our review, we examined maternal age, gestational age at the time of delivery, parity, type of pregnancy, placental weight, ultrasound features of the placenta, macroscopic examination and tumor size, microscopic examination, immunostaining, maternal beta-human chorionic gonadotropin, fetal and maternal outcome. Eight manuscripts were detected. They are all case reports. The macroscopic characteristics of the lesions were represented by the presence of a grey-yellow-white color well-demarcated round nodule. Microscopically, all the authors described typical aspects of malignancy as a high rate of mitosis, nuclear atypia and necrotic areas. In some cases, the presence of AE1/AE3 cytoplasmic positivity, p63 nuclear staining, and beta-human chorionic gonadotropin (BHCG) were reported. A good fetal outcome was reported in all cases of newborns with normal birth weight, except one with fetal growth restriction. Maternal outcome was good in all cases except one with maternal lung metastasis three months after delivery. The clinical course has probably underestimated the real incidence of the pathology. Only greater knowledge of its histology and its clinical course will allow us to evaluate the real prevalence of the disease.
PubMed: 37176506
DOI: 10.3390/jcm12093065 -
Frontiers in Oncology 2022The indications for sentinel lymph node biopsy (SLNB) for thin melanoma are still unclear. This meta-analysis aims to determine the positive rate of SLNB in thin...
BACKGROUND
The indications for sentinel lymph node biopsy (SLNB) for thin melanoma are still unclear. This meta-analysis aims to determine the positive rate of SLNB in thin melanoma and to summarize the predictive value of different high-risk features for positive results of SLNB.
METHODS
Four databases were searched for literature on SLNB performed in patients with thin melanoma published between January 2000 and December 2020. The overall positive rate and positive rate of each high-risk feature were calculated and obtained with 95% confidence intervals (CIs). Both unadjusted odds ratios (ORs) and adjusted ORs (AORs) of high-risk features were analyzed. Pooled effects were estimated using random-effects model meta-analyses.
RESULTS
Sixty-six studies reporting 38,844 patients with thin melanoma who underwent SLNB met the inclusion criteria. The pooled positive rate of SLNB was 5.1% [95% confidence interval (CI) 4.9%-5.3%]. Features significantly predicted a positive result of SLNB were thickness≥0.8 mm [AOR 1.94 (95%CI 1.28-2.95); positive rate 7.0% (95%CI 6.0-8.0%)]; ulceration [AOR 3.09 (95%CI 1.75-5.44); positive rate 4.2% (95%CI 1.8-7.2%)]; mitosis rate >0/mm2 [AOR 1.63 (95%CI 1.13-2.36); positive rate 7.7% (95%CI 6.3-9.1%)]; microsatellites [OR 3.8 (95%CI 1.38-10.47); positive rate 16.6% (95%CI 2.4-36.6%)]; and vertical growth phase [OR 2.76 (95%CI 1.72-4.43); positive rate 8.1% (95%CI 6.3-10.1%)].
CONCLUSIONS
The overall positive rate of SLNB in thin melanoma was 5.1%. The strongest predictor for SLN positivity identified was microsatellites on unadjusted analysis and ulceration on adjusted analysis. Breslow thickness ≥0.8 mm and mitosis rate >0/mm both predict SLN positivity in adjusted analysis and increase the positive rate to 7.0% and 7.7%. We suggest patients with thin melanoma with the above high-risk features should be considered for giving an SLNB.
PubMed: 35155254
DOI: 10.3389/fonc.2022.817510 -
Scientific Reports Sep 2015Many types of KIT mutations have been observed in gastrointestinal stromal tumors (GISTs), but their prognostic and predictive significance are still unclear. A... (Meta-Analysis)
Meta-Analysis Review
Many types of KIT mutations have been observed in gastrointestinal stromal tumors (GISTs), but their prognostic and predictive significance are still unclear. A meta-analysis and literature review were conducted to estimate the contribution of KIT mutations in prognostic parameters and clinic-pathological significance of GISTs. A total of 18 relevant articles from PubMed, EMBASE and Web of Science databases were included in this study. The frequency of KIT mutation was significantly increased in the GIST patients with higher mitosis (≥5/50 high-power fields (HPFs) and larger size (≥5 cm) of tumors than in those with lower MI (≤5/50HPFs) and smaller size (≤5 cm) of GISTs respectively. The rate of KIT mutation was not significantly changed between GISTs in stomachs and in small intestines. KIT mutational status has prognostic significance for patients' outcome. GIST patients with KIT exon 9 mutations have higher risk of progression than those with exon 11 mutations. 5 year relapse-free survival (RFS) rate was significantly higher in patients with KIT exon 11 deletion than in those with other type of KIT exon 11 mutations. The deletion involving KIT exon 11, particularly codons 557-558, is a valuable predictor of prognosis for patients with GISTs.
Topics: Exons; Gastrointestinal Stromal Tumors; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Mutation; Odds Ratio; Prognosis; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Risk
PubMed: 26349547
DOI: 10.1038/srep13718 -
Cancer Cell International 2020One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related... (Review)
Review
One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related proteins gives tumor cells their invasive, metastatic, drug-resistance, and anti-apoptotic abilities. Recently, an increasing number of cell cycle-associated proteins have become the candidate biomarkers for early diagnosis of malignant tumors and potential targets for cancer therapies. As an important cell cycle regulatory protein, Cell Division Cycle 25C (CDC25C) participates in regulating G2/M progression and in mediating DNA damage repair. CDC25C is a cyclin of the specific phosphatase family that activates the cyclin B1/CDK1 complex in cells for entering mitosis and regulates G2/M progression and plays an important role in checkpoint protein regulation in case of DNA damage, which can ensure accurate DNA information transmission to the daughter cells. The regulation of CDC25C in the cell cycle is affected by multiple signaling pathways, such as cyclin B1/CDK1, PLK1/Aurora A, ATR/CHK1, ATM/CHK2, CHK2/ERK, Wee1/Myt1, p53/Pin1, and ASK1/JNK-/38. Recently, it has evident that changes in the expression of CDC25C are closely related to tumorigenesis and tumor development and can be used as a potential target for cancer treatment. This review summarizes the role of CDC25C phosphatase in regulating cell cycle. Based on the role of CDC25 family proteins in the development of tumors, it will become a hot target for a new generation of cancer treatments.
PubMed: 32518522
DOI: 10.1186/s12935-020-01304-w