The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer i...The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer is the most common malignant tumor in women and one of the leading causes of cancer-related deaths.展开更多
Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and ...Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications.However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.展开更多
Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors(especially...Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors(especially HER1/EGFR and HER2/ERBB2) are involved in disease progression; hence, strategies to inhibit their action could prove advantageous in ovarian cancer patients,especially in patients resistant to first line therapy. Monoclonal antibodies and tyrosine kinase inhibitors are two classes of drugs that act on these receptors. They have demonstrated valuable antitumor activity in multiple cancers and their possible use in ovarian cancer continues to be studied. In this review, we discuss the human epidermal growth factor receptor family; review emerging clinical studies on monoclonal antibodies and tyrosine kinase inhibitors targeting these receptors in ovarian cancer patients; and propose future research possibilities in this area.展开更多
AIM:To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.METHODS:The study group included 45 patients who underwent curative gastrectomies from 1995 t...AIM:To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.METHODS:The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available.Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples,preserving the small RNA fraction.Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection.The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR).Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group,n=14,31%) and those who did not (good-prognosis group,n=31,69%).RESULTS:Three miRs,miR-451,miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P<0.0002,0.0027 and 0.0046 respectively).High expression of each miR was associated with poorer prognosis for both recurrence and survival.Using miR-451,the positive predictive value for non-recurrence was 100% (13/13).The expression of the differential miRs was verified by qRT-PCR,showing high correlation to the microarray data and similar separation into prognosis groups.CONCLUSION:This study identified three miRs,miR-451,miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer.Of these,miR-451 had the strongest prognostic impact.展开更多
MicroRNAs have become recognized as key players in the development of cancer. They are a family of small non-coding RNAs that can negatively regulate the expression of cancer-related genes by sequence-selective target...MicroRNAs have become recognized as key players in the development of cancer. They are a family of small non-coding RNAs that can negatively regulate the expression of cancer-related genes by sequence-selective targeting of mRNAs, leading to either mRNA degradation or translational repression. Lung cancer is the leading cause of cancer-related death worldwide with a substantially low survival rate. MicroRNAs have been confirmed to play roles in lung cancer develop-ment, epithelial-mesenchymal transition and response to therapy. They are also being studied for their future use as diagnostic and prognostic biomarkers and as potential therapeutic targets. In this review we focus on the role of dysregulated microRNA expression in lung tumorigenesis. We also discuss the role of microRNAs in therapeutic resistance and as biomarkers. We further look into the progress made and challenges remaining in using microRNAs for therapy in lung cancer.展开更多
Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the ...Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the estrogen receptor(ER) as the direct(for tamoxifen and fulvestrant) or indirect(for aromatase inhibitors) target molecule for endocrine therapy remains the foremost biomarker and determinant of response. However, ER expression only poorly predicts outcome and further indicators of response or resistance are required. The development and application of molecular signature assays such as Oncotype Dx, Prosigna, Mammaprint and Endopredict have provided valuable information on prognosis and these are being used to support clinical decision making on whether endocrine therapy alone alongside surgery is sufficient for ER-positive early stage breast cancers or whether combination of endocrine with chemotherapy are also warranted. Ki67, the proliferation marker, has been widely used in the neo-adjuvant(pre-operative) setting to help predict response and long term outcome. Gene expression studies within the same setting have allowed monitoring of changes of potential predictive markers. These have identified frequent changes in estrogenregulated and proliferation genes. Specific molecules such as mutant ER may also prove helpful biomarkers in predicting outcome and monitoring response to treatment.展开更多
There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a...There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.展开更多
In the published article~, some errors appeared on page 238, Figure 1, and reference list. The editors and the authors apologize for the errors and for any confusion they may have caused. On page238, the sentence of ...In the published article~, some errors appeared on page 238, Figure 1, and reference list. The editors and the authors apologize for the errors and for any confusion they may have caused. On page238, the sentence of ＂affecting 20% and 17.5% of cases＂ should be changed to ＂and that inactivation of these genes occurs in 17.5% and 20% of cases＂.展开更多
The principal breast cancer treatment approach has long been surgical removal of the primary breast lesions and regional lymph nodes,particularly the axillary lymph nodes.However,the advent of minimally invasive diagn...The principal breast cancer treatment approach has long been surgical removal of the primary breast lesions and regional lymph nodes,particularly the axillary lymph nodes.However,the advent of minimally invasive diagnostic techniques,such as sentinel lymph node biopsy(SLNB),has markedly diminished the extent of surgery required for regional lymph nodes.展开更多
Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately m...Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).展开更多
Nuclear accumulation of active Smad complexes is crucial for transduction of transforming growth factor β （TGF-β）- superfamily signals from transmembrane receptors into the nucleus. It is now clear that the nucleo...Nuclear accumulation of active Smad complexes is crucial for transduction of transforming growth factor β （TGF-β）- superfamily signals from transmembrane receptors into the nucleus. It is now clear that the nucleocytoplasmic distributions of Smads, in both the absence and the presence of a TGF-β-superfamily signal, are not static, but instead the Smads are continuously shuttling between the nucleus and the cytoplasm in both conditions. This article presents the evidence for continuous nucleocytoplasmic shuttling of Smads. It then reviews different mechanisms that have been proposed to mediate Smad nuclear import and export, and discusses how the Smad steady-state distributions in the absence and the presence of a TGF-β-superfamily signal are established. Finally, the biological relevance of continuous nucleocytoplasmic shuttling for signaling by TGF-β superfamily members is discussed.展开更多
AIM： To study the correlation between the patterns of subcellular expression of p16 and CDK4 in colorectal epithelia in the normal-adenoma-carcinoma sequence.METHODS： Paraffin sections of 43 cases of normal colorect...AIM： To study the correlation between the patterns of subcellular expression of p16 and CDK4 in colorectal epithelia in the normal-adenoma-carcinoma sequence.METHODS： Paraffin sections of 43 cases of normal colorectal epithelia and corresponding adenomas as well as carcinomas were analysed immunocytochemically for subcellular expression of p16 and CDK4 proteins.RESULTS： Most carcinomas showed more cytoplasmic overexpression for p16 and CDK4 than the adenomas from which they arised or the adjacent normal mucosa. Most normal or non-neoplastic epithelia showed more p16 and CDK4 expression in the nucleus than their adjacent adenomas and carcinomas. There was a significant difference between the subcellular expression pattern of p16 and CDK4 in normal-adenoma-carcinoma sequence epithelia （P 〈 0.001）. Neither p16 nor CDK4 subcellular patterns correlated with histological grade or Dukes＇ stage.CONCLUSION： Interaction of expression of p16 and CDK4 plays an important role in the Rb/p16 pathway.Overexpression of p16 and CDK4 in the cytoplasm, as well as loss expression of p16 in the nucleusmighlc be important in the evolution of colorectal carcinoma from adenoma and, of adenoma from normal epitheiia.展开更多
Preventing the propagation of damaged cells is a central component of tumour suppression. A key factor in this process is the transcription factor p53 - a fact exemplified by its frequent inactivation in human cancer....Preventing the propagation of damaged cells is a central component of tumour suppression. A key factor in this process is the transcription factor p53 - a fact exemplified by its frequent inactivation in human cancer. Since its discovery, over forty thousand reports have been published investigating p53 function and regulation. It is known that p53 mediates the expression of a diverse set of target genes which are broadly grouped by the biological response they provoke, with the best characterized being the induction of growth arrest, during which cellular damage is repaired, or the induction of apoptosis, which serves to eradicate damaged cells that may otherwise go on to form a tumour .展开更多
AIM： To investigate the correlation between tissue ST6Gal I and serum msAFP in HCC patients, and to investigate their prognostic significance. METHODS： Preoperative sera, paired tumorous and non-tumorous tissues wer...AIM： To investigate the correlation between tissue ST6Gal I and serum msAFP in HCC patients, and to investigate their prognostic significance. METHODS： Preoperative sera, paired tumorous and non-tumorous tissues were collected from 19 consecutive patients who had undergone surgical resection of HCC. ST6Gal I activities in the tissues were measured by an in vitro microsomal enzyme activity assay. The percentages of tumor-specific msAFP in the sera were also estimated by an isoelectric focusing-immunoblotting assay. RESULTS： The tumor ST6Gal I activity was negatively correlated with serum msAFP percentage （r = -0.53, P = 0.019）. Both decreased tumor ST6Gal I activity and increased serum msAFP percentage were associated with poor tumor cell differentiation. Univariate analyses showed that both decreased tumor ST6Gal I activity （P = 0.028）, increased serum msAFP percentage （P = 0.034） and poor tumor cell differentiation （P = 0.031）were associated with shorter overall survival. Multivariate analysis using the Cox regression model showed that the preoperative serum msAFP percentage （P = 0.022） and tumor cell differentiation status （P = 0.048） were independent prognostic indicators for patient overall survival. CONCLUSION： Our results indicate that the presence of msAFP in blood circulation is associated with a decreased activity of ST6Gal I activity in HCC. Both tissue ST6Gal I and serum msAFP are potential prognostic markers for patients with operable HCC.展开更多
The first cases of coronavirus disease 2019(COVID-19)were detected in Wuhan,China,in December 2019.Since this time a concerted global effort of research and observational data gathering has meant that a great deal has...The first cases of coronavirus disease 2019(COVID-19)were detected in Wuhan,China,in December 2019.Since this time a concerted global effort of research and observational data gathering has meant that a great deal has been learnt about the impact of COVID-19 in patients with lymphoid malignancies.Approximately onethird of patients with lymphoid malignancies who acquire COVID-19 and have it severely enough to require hospital assessment will die from this infection.Major risk factors for a poor outcome are age and co-morbidities,but when these are taken into account lymphoma patients have a slightly greater than 2-fold increased risk compared to the general population.Notably,despite early concerns regarding the particular vulnerability of lymphoma patients due to the immunosuppressive effects of therapy,active treatment,including B-cell depleting agents such as rituximab,do not appear to be associated with an increased risk of a poorer outcome.Indeed,some treatments such as ibrutinib may be beneficial due to their modulation of the potential fatal hyperinflammatory phase of infection.There are risks associated with hemopoietic stem cell transplantation,but the collective experience is that these can be minimized by preventive strategies and that the majority of transplant recipients with COVID-19 infection will survive.Many questions remain including those regarding the outcome of COVID-19 infection in the rarer lymphoid malignancies and the efficacy of COVID-19 vaccines in lymphoma patients.This review aims to discuss these issues and present a summary of the current knowledge of the impact of COVID-19 in lymphoid malignancies.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.81672638)。
文摘The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer is the most common malignant tumor in women and one of the leading causes of cancer-related deaths.
文摘Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications.However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.
基金The work disclosed in this publication is partially funded by the Endeavour Scholarship Scheme (Malta) Scholarships are part-financed by the European Union–European Social Fund (ESF)–Operational Program II–Cohesion Policy 2014–2020 "Investing in human capital to create more opportunities and promote the well-being of society"
文摘Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors(especially HER1/EGFR and HER2/ERBB2) are involved in disease progression; hence, strategies to inhibit their action could prove advantageous in ovarian cancer patients,especially in patients resistant to first line therapy. Monoclonal antibodies and tyrosine kinase inhibitors are two classes of drugs that act on these receptors. They have demonstrated valuable antitumor activity in multiple cancers and their possible use in ovarian cancer continues to be studied. In this review, we discuss the human epidermal growth factor receptor family; review emerging clinical studies on monoclonal antibodies and tyrosine kinase inhibitors targeting these receptors in ovarian cancer patients; and propose future research possibilities in this area.
文摘AIM:To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.METHODS:The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available.Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples,preserving the small RNA fraction.Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection.The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR).Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group,n=14,31%) and those who did not (good-prognosis group,n=31,69%).RESULTS:Three miRs,miR-451,miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P<0.0002,0.0027 and 0.0046 respectively).High expression of each miR was associated with poorer prognosis for both recurrence and survival.Using miR-451,the positive predictive value for non-recurrence was 100% (13/13).The expression of the differential miRs was verified by qRT-PCR,showing high correlation to the microarray data and similar separation into prognosis groups.CONCLUSION:This study identified three miRs,miR-451,miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer.Of these,miR-451 had the strongest prognostic impact.
文摘MicroRNAs have become recognized as key players in the development of cancer. They are a family of small non-coding RNAs that can negatively regulate the expression of cancer-related genes by sequence-selective targeting of mRNAs, leading to either mRNA degradation or translational repression. Lung cancer is the leading cause of cancer-related death worldwide with a substantially low survival rate. MicroRNAs have been confirmed to play roles in lung cancer develop-ment, epithelial-mesenchymal transition and response to therapy. They are also being studied for their future use as diagnostic and prognostic biomarkers and as potential therapeutic targets. In this review we focus on the role of dysregulated microRNA expression in lung tumorigenesis. We also discuss the role of microRNAs in therapeutic resistance and as biomarkers. We further look into the progress made and challenges remaining in using microRNAs for therapy in lung cancer.
文摘Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the estrogen receptor(ER) as the direct(for tamoxifen and fulvestrant) or indirect(for aromatase inhibitors) target molecule for endocrine therapy remains the foremost biomarker and determinant of response. However, ER expression only poorly predicts outcome and further indicators of response or resistance are required. The development and application of molecular signature assays such as Oncotype Dx, Prosigna, Mammaprint and Endopredict have provided valuable information on prognosis and these are being used to support clinical decision making on whether endocrine therapy alone alongside surgery is sufficient for ER-positive early stage breast cancers or whether combination of endocrine with chemotherapy are also warranted. Ki67, the proliferation marker, has been widely used in the neo-adjuvant(pre-operative) setting to help predict response and long term outcome. Gene expression studies within the same setting have allowed monitoring of changes of potential predictive markers. These have identified frequent changes in estrogenregulated and proliferation genes. Specific molecules such as mutant ER may also prove helpful biomarkers in predicting outcome and monitoring response to treatment.
文摘There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
文摘In the published article~, some errors appeared on page 238, Figure 1, and reference list. The editors and the authors apologize for the errors and for any confusion they may have caused. On page238, the sentence of ＂affecting 20% and 17.5% of cases＂ should be changed to ＂and that inactivation of these genes occurs in 17.5% and 20% of cases＂.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81672638 and W2421095)National Natural Science Foundation of Shandong Province(Grant No.ZR2024LMB011)Collaborative Academic Innovation Project of Shandong Cancer Hospital(Grant No.GF003)。
文摘The principal breast cancer treatment approach has long been surgical removal of the primary breast lesions and regional lymph nodes,particularly the axillary lymph nodes.However,the advent of minimally invasive diagnostic techniques,such as sentinel lymph node biopsy(SLNB),has markedly diminished the extent of surgery required for regional lymph nodes.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82573747,82172873,W2421095,and 82503888)National Science and Technology Major Project(Grant No.2025ZD0543900)+2 种基金Natural Science Foundation of Shandong Province(Grant Nos.ZR2024LMB011 and ZR2024QH058)Taishan Scholars Program of Shandong Province(Grant No.tsqn202211337)Collaborative Academic Innovation Project of Shandong Cancer Hospital(Grant No.GF003).
文摘Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).
文摘Nuclear accumulation of active Smad complexes is crucial for transduction of transforming growth factor β （TGF-β）- superfamily signals from transmembrane receptors into the nucleus. It is now clear that the nucleocytoplasmic distributions of Smads, in both the absence and the presence of a TGF-β-superfamily signal, are not static, but instead the Smads are continuously shuttling between the nucleus and the cytoplasm in both conditions. This article presents the evidence for continuous nucleocytoplasmic shuttling of Smads. It then reviews different mechanisms that have been proposed to mediate Smad nuclear import and export, and discusses how the Smad steady-state distributions in the absence and the presence of a TGF-β-superfamily signal are established. Finally, the biological relevance of continuous nucleocytoplasmic shuttling for signaling by TGF-β superfamily members is discussed.
文摘AIM： To study the correlation between the patterns of subcellular expression of p16 and CDK4 in colorectal epithelia in the normal-adenoma-carcinoma sequence.METHODS： Paraffin sections of 43 cases of normal colorectal epithelia and corresponding adenomas as well as carcinomas were analysed immunocytochemically for subcellular expression of p16 and CDK4 proteins.RESULTS： Most carcinomas showed more cytoplasmic overexpression for p16 and CDK4 than the adenomas from which they arised or the adjacent normal mucosa. Most normal or non-neoplastic epithelia showed more p16 and CDK4 expression in the nucleus than their adjacent adenomas and carcinomas. There was a significant difference between the subcellular expression pattern of p16 and CDK4 in normal-adenoma-carcinoma sequence epithelia （P 〈 0.001）. Neither p16 nor CDK4 subcellular patterns correlated with histological grade or Dukes＇ stage.CONCLUSION： Interaction of expression of p16 and CDK4 plays an important role in the Rb/p16 pathway.Overexpression of p16 and CDK4 in the cytoplasm, as well as loss expression of p16 in the nucleusmighlc be important in the evolution of colorectal carcinoma from adenoma and, of adenoma from normal epitheiia.
文摘Preventing the propagation of damaged cells is a central component of tumour suppression. A key factor in this process is the transcription factor p53 - a fact exemplified by its frequent inactivation in human cancer. Since its discovery, over forty thousand reports have been published investigating p53 function and regulation. It is known that p53 mediates the expression of a diverse set of target genes which are broadly grouped by the biological response they provoke, with the best characterized being the induction of growth arrest, during which cellular damage is repaired, or the induction of apoptosis, which serves to eradicate damaged cells that may otherwise go on to form a tumour .
基金Supported by Central Allocation Grant CUHK 2/02C from the University Grants Committee of Hong Kong the Direct Grant for Research (2040750) from the Chinese University of Hong Kong
文摘AIM： To investigate the correlation between tissue ST6Gal I and serum msAFP in HCC patients, and to investigate their prognostic significance. METHODS： Preoperative sera, paired tumorous and non-tumorous tissues were collected from 19 consecutive patients who had undergone surgical resection of HCC. ST6Gal I activities in the tissues were measured by an in vitro microsomal enzyme activity assay. The percentages of tumor-specific msAFP in the sera were also estimated by an isoelectric focusing-immunoblotting assay. RESULTS： The tumor ST6Gal I activity was negatively correlated with serum msAFP percentage （r = -0.53, P = 0.019）. Both decreased tumor ST6Gal I activity and increased serum msAFP percentage were associated with poor tumor cell differentiation. Univariate analyses showed that both decreased tumor ST6Gal I activity （P = 0.028）, increased serum msAFP percentage （P = 0.034） and poor tumor cell differentiation （P = 0.031）were associated with shorter overall survival. Multivariate analysis using the Cox regression model showed that the preoperative serum msAFP percentage （P = 0.022） and tumor cell differentiation status （P = 0.048） were independent prognostic indicators for patient overall survival. CONCLUSION： Our results indicate that the presence of msAFP in blood circulation is associated with a decreased activity of ST6Gal I activity in HCC. Both tissue ST6Gal I and serum msAFP are potential prognostic markers for patients with operable HCC.
文摘The first cases of coronavirus disease 2019(COVID-19)were detected in Wuhan,China,in December 2019.Since this time a concerted global effort of research and observational data gathering has meant that a great deal has been learnt about the impact of COVID-19 in patients with lymphoid malignancies.Approximately onethird of patients with lymphoid malignancies who acquire COVID-19 and have it severely enough to require hospital assessment will die from this infection.Major risk factors for a poor outcome are age and co-morbidities,but when these are taken into account lymphoma patients have a slightly greater than 2-fold increased risk compared to the general population.Notably,despite early concerns regarding the particular vulnerability of lymphoma patients due to the immunosuppressive effects of therapy,active treatment,including B-cell depleting agents such as rituximab,do not appear to be associated with an increased risk of a poorer outcome.Indeed,some treatments such as ibrutinib may be beneficial due to their modulation of the potential fatal hyperinflammatory phase of infection.There are risks associated with hemopoietic stem cell transplantation,but the collective experience is that these can be minimized by preventive strategies and that the majority of transplant recipients with COVID-19 infection will survive.Many questions remain including those regarding the outcome of COVID-19 infection in the rarer lymphoid malignancies and the efficacy of COVID-19 vaccines in lymphoma patients.This review aims to discuss these issues and present a summary of the current knowledge of the impact of COVID-19 in lymphoid malignancies.
