Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the avail...Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator （CFTR） gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach： （i） first, a reverse dot-blot analysis was performed to detect mutations with regional impact; （ii） next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and （iii） finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.展开更多
Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applic...Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.展开更多
A cohort of 404 patients referred for hereditary neuropathy with liability to pressure palsies was tested initially for the common PMP22 whole gene deletion. 94 whole gene deletions were detected, plus three partial g...A cohort of 404 patients referred for hereditary neuropathy with liability to pressure palsies was tested initially for the common PMP22 whole gene deletion. 94 whole gene deletions were detected, plus three partial gene deletions, and the remaining 307 patients were screened for PMP22 point mutations. Nine point mutations were identified (8.5% of all mutations), eight of which were in exon 5, suggesting a point mutation hotspot for individuals with this condition. Sequencing analysis of PMP22 exon 5 should therefore be included as a routine diagnostic test for gene deletion-negative patients.展开更多
The so-calledPhiladelphia(Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 and the 3' part of the ...The so-calledPhiladelphia(Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 and the 3' part of the ABL1 gene on chromosome 9. An additional acquired monosomy 7 or deletion of 7q is associated with poor prognosis in a variety of myeloid disorders. Here we report a novel Ph chromosome positive CML case with a ring chromosome 7 [r(7)]. Immunophenotyping was compatible with CML, although 4.5% of total leucocytes appeared like acute myelogeneous leukemia (AML) subtype M2. The r(7) was characterized in detail by array-proven multicolor banding (aMCB), the latter being of enormous significance to characterize breakpoint regions in detail. Underlying mechanisms and prognostic are discussed, as ring chromosomes are rare cytogenetic abnormalities in hematopoietic malignancies.展开更多
Blepharoptosis (ptosis) is defined as the abnormal drooping of the upper eyelid and is a feature of many conditions. It can be in isolated or syndromic form, bilateral or unilateral and congenital or acquired. Previou...Blepharoptosis (ptosis) is defined as the abnormal drooping of the upper eyelid and is a feature of many conditions. It can be in isolated or syndromic form, bilateral or unilateral and congenital or acquired. Previously we have carried out linkage analysis on a family with dominantly inherited congenital bilateral isolated ptosis and found the condition to be linked to a region of approximately 20 megabases of chromosome Xq24-Xq27.1 with a cumulative LOD score of 5.89. We now describe further analysis using array comparative genomic hybridisation (array CGH), fluorescence in situ hybridisation (FISH), long range PCR and sequencing. This has enabled us to identify and characterise at the level of DNA sequence an insertional duplication and rearrangement involving chromosomes 1p21.3 and a small quasipalindromic sequence in Xq27.1, disruption of which has been associated with other phenotypes but which is cosegregating with X-linked congenital bilateral isolated ptosis in this family. This work highlights the significance of the small quasipalindromic sequence in genomic rearrangements involving Xq27.1 and the importance of comprehensive molecular and molecular cytogenetic investigations to fully characterise genomic structural complexity.展开更多
Cancer Stem Cells (CSC) have the ability to self-renew and are present in most tissues including breast, brain, lung, prostates, testis, ovary, esophagus, colon, and liver. Their origin is yet to be discovered, though...Cancer Stem Cells (CSC) have the ability to self-renew and are present in most tissues including breast, brain, lung, prostates, testis, ovary, esophagus, colon, and liver. Their origin is yet to be discovered, though a series of hypotheses have been proposed in this regard. CSCs play a role in not only the creation of cancer, but also in its evolution, metastasis, and recurrence. CSCs have an important role in cancer therapy and the resistance towards chemotherapeutic agents. This article reviews the characteristics of cancer stem cells in terms of origin, resistance towards chemotherapy, methods of isolation, and cancer therapy.展开更多
BACKGROUND Lateral pelvic lymph node(LLN)metastasis(LLNM)occur in up to 28%of patients with low rectal tumours.While prophylactic lateral pelvic lymph node dissection(LLND)has been abandoned by most western institutio...BACKGROUND Lateral pelvic lymph node(LLN)metastasis(LLNM)occur in up to 28%of patients with low rectal tumours.While prophylactic lateral pelvic lymph node dissection(LLND)has been abandoned by most western institutions in the era of neoadjuvant chemoradiation therapy(CRT),the role of selective LLND in patients with enlarged LLN on pre-CRT imaging remains unclear.Some studies have shown improved survival and recurrence outcomes when LLNs show"response"to CRT.However,no management algorithm exists to differentiate treatment for"responders"vs"non-responders".AIM To determine if selective LLND in patients with enlarged LLNs results in improved survival and recurrence outcomes.METHODS A systemic search of Pub Med and Embase databases for studies reporting on patients with synchronous radiologically suspicious LLNM(s-LLNM)in rectal cancer receiving preoperative-CRT was performed.RESULTS Fifteen retrospective,single-centre studies were included.793 patients with sLLNM were evaluated:456 underwent TME while 337 underwent TME with7,LLND post-CRT.In the TME group,local recurrence(LR)rates range from 12.5%to 36%.Five-year disease free survival(DFS)was 42%to 75%.In the TME with LLND group,LR rates were 0%to 6%.Five years DFS was 41.2%to 100%.Radiological response was seen in 58%.Pathologically positive LLN was found in up to 94%of non-responders vs 0%to 20%in responders.Young age,low tumour location and radiological non-response were associated with final positive LLNM and lowered DFS.CONCLUSION LLND is associated with local control in patients with s-LLNM.It can be performed in radiological non-responders given a large majority represent true LLNM.Its role in radiological responders should be considered in selected high risk patients.展开更多
Background: Myelodysplastic syndromes (MDS) are subtypes of hematological disorders which are known to have partial bone marrow dysplasia, peripheral cytopenia, and later on an increased risk to develop acute myeloid ...Background: Myelodysplastic syndromes (MDS) are subtypes of hematological disorders which are known to have partial bone marrow dysplasia, peripheral cytopenia, and later on an increased risk to develop acute myeloid leukemia. Chromosomal aberrations are detected in ~50% of cases of de novo MDS cases and the most common chromosomal abnormalities of this entity include complete or partial monosomy of chromosomes 5 and 7, partial deletion of 20q and 12p, trisomy 8, and 11q23 aberrations. A few primary and/or secondary MDS cases combined with other cancer have been reported. Case Presentation: We report here an adult MDS associated with squamous cell carcinoma (SCC). G-banding and array-proven multicolor banding (aMCB) revealed an unbalanced translocation der(7)t(1;7)(q21;q21), which led to 1q partial trisomy and 7q partial monosomy. Immunophenotype of this case was consistent with refractory anemia with excess of blasts (RAEB-2) according to World Health Organization (WHO) classification. Conclusions: As far as we know, this is the first adult MDS case associated with SCC and an unbalanced translocation t(1;7). Our patient received first cycle of azacitidine treatment and he showed bilateral pleural effusion as a secondary event. This toxicity is not limited to the first cycle as in previous MDS cases;our case is the first one to shown this toxicity as a secondary event of azacitidine treatment. As less than 10 cytogenetcially comparable cases without SCC were reported before in male MDS, we carefully conclude that this cytogenetic aberration may be a hint on a new gender associated MDS subgroup.展开更多
文摘Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator （CFTR） gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach： （i） first, a reverse dot-blot analysis was performed to detect mutations with regional impact; （ii） next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and （iii） finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.
文摘Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.
文摘A cohort of 404 patients referred for hereditary neuropathy with liability to pressure palsies was tested initially for the common PMP22 whole gene deletion. 94 whole gene deletions were detected, plus three partial gene deletions, and the remaining 307 patients were screened for PMP22 point mutations. Nine point mutations were identified (8.5% of all mutations), eight of which were in exon 5, suggesting a point mutation hotspot for individuals with this condition. Sequencing analysis of PMP22 exon 5 should therefore be included as a routine diagnostic test for gene deletion-negative patients.
文摘The so-calledPhiladelphia(Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 and the 3' part of the ABL1 gene on chromosome 9. An additional acquired monosomy 7 or deletion of 7q is associated with poor prognosis in a variety of myeloid disorders. Here we report a novel Ph chromosome positive CML case with a ring chromosome 7 [r(7)]. Immunophenotyping was compatible with CML, although 4.5% of total leucocytes appeared like acute myelogeneous leukemia (AML) subtype M2. The r(7) was characterized in detail by array-proven multicolor banding (aMCB), the latter being of enormous significance to characterize breakpoint regions in detail. Underlying mechanisms and prognostic are discussed, as ring chromosomes are rare cytogenetic abnormalities in hematopoietic malignancies.
文摘Blepharoptosis (ptosis) is defined as the abnormal drooping of the upper eyelid and is a feature of many conditions. It can be in isolated or syndromic form, bilateral or unilateral and congenital or acquired. Previously we have carried out linkage analysis on a family with dominantly inherited congenital bilateral isolated ptosis and found the condition to be linked to a region of approximately 20 megabases of chromosome Xq24-Xq27.1 with a cumulative LOD score of 5.89. We now describe further analysis using array comparative genomic hybridisation (array CGH), fluorescence in situ hybridisation (FISH), long range PCR and sequencing. This has enabled us to identify and characterise at the level of DNA sequence an insertional duplication and rearrangement involving chromosomes 1p21.3 and a small quasipalindromic sequence in Xq27.1, disruption of which has been associated with other phenotypes but which is cosegregating with X-linked congenital bilateral isolated ptosis in this family. This work highlights the significance of the small quasipalindromic sequence in genomic rearrangements involving Xq27.1 and the importance of comprehensive molecular and molecular cytogenetic investigations to fully characterise genomic structural complexity.
文摘Cancer Stem Cells (CSC) have the ability to self-renew and are present in most tissues including breast, brain, lung, prostates, testis, ovary, esophagus, colon, and liver. Their origin is yet to be discovered, though a series of hypotheses have been proposed in this regard. CSCs play a role in not only the creation of cancer, but also in its evolution, metastasis, and recurrence. CSCs have an important role in cancer therapy and the resistance towards chemotherapeutic agents. This article reviews the characteristics of cancer stem cells in terms of origin, resistance towards chemotherapy, methods of isolation, and cancer therapy.
文摘BACKGROUND Lateral pelvic lymph node(LLN)metastasis(LLNM)occur in up to 28%of patients with low rectal tumours.While prophylactic lateral pelvic lymph node dissection(LLND)has been abandoned by most western institutions in the era of neoadjuvant chemoradiation therapy(CRT),the role of selective LLND in patients with enlarged LLN on pre-CRT imaging remains unclear.Some studies have shown improved survival and recurrence outcomes when LLNs show"response"to CRT.However,no management algorithm exists to differentiate treatment for"responders"vs"non-responders".AIM To determine if selective LLND in patients with enlarged LLNs results in improved survival and recurrence outcomes.METHODS A systemic search of Pub Med and Embase databases for studies reporting on patients with synchronous radiologically suspicious LLNM(s-LLNM)in rectal cancer receiving preoperative-CRT was performed.RESULTS Fifteen retrospective,single-centre studies were included.793 patients with sLLNM were evaluated:456 underwent TME while 337 underwent TME with7,LLND post-CRT.In the TME group,local recurrence(LR)rates range from 12.5%to 36%.Five-year disease free survival(DFS)was 42%to 75%.In the TME with LLND group,LR rates were 0%to 6%.Five years DFS was 41.2%to 100%.Radiological response was seen in 58%.Pathologically positive LLN was found in up to 94%of non-responders vs 0%to 20%in responders.Young age,low tumour location and radiological non-response were associated with final positive LLNM and lowered DFS.CONCLUSION LLND is associated with local control in patients with s-LLNM.It can be performed in radiological non-responders given a large majority represent true LLNM.Its role in radiological responders should be considered in selected high risk patients.
文摘Background: Myelodysplastic syndromes (MDS) are subtypes of hematological disorders which are known to have partial bone marrow dysplasia, peripheral cytopenia, and later on an increased risk to develop acute myeloid leukemia. Chromosomal aberrations are detected in ~50% of cases of de novo MDS cases and the most common chromosomal abnormalities of this entity include complete or partial monosomy of chromosomes 5 and 7, partial deletion of 20q and 12p, trisomy 8, and 11q23 aberrations. A few primary and/or secondary MDS cases combined with other cancer have been reported. Case Presentation: We report here an adult MDS associated with squamous cell carcinoma (SCC). G-banding and array-proven multicolor banding (aMCB) revealed an unbalanced translocation der(7)t(1;7)(q21;q21), which led to 1q partial trisomy and 7q partial monosomy. Immunophenotype of this case was consistent with refractory anemia with excess of blasts (RAEB-2) according to World Health Organization (WHO) classification. Conclusions: As far as we know, this is the first adult MDS case associated with SCC and an unbalanced translocation t(1;7). Our patient received first cycle of azacitidine treatment and he showed bilateral pleural effusion as a secondary event. This toxicity is not limited to the first cycle as in previous MDS cases;our case is the first one to shown this toxicity as a secondary event of azacitidine treatment. As less than 10 cytogenetcially comparable cases without SCC were reported before in male MDS, we carefully conclude that this cytogenetic aberration may be a hint on a new gender associated MDS subgroup.
