Lung cancer is the leading cause of cancer death worldwide.Majority of newly diagnosed lung cancers are non-small cell lung cancer(NSCLC), of which up to half are considered locally advanced at the time of diagnosis.P...Lung cancer is the leading cause of cancer death worldwide.Majority of newly diagnosed lung cancers are non-small cell lung cancer(NSCLC), of which up to half are considered locally advanced at the time of diagnosis.Patients with locally advanced stage Ⅲ NSCLC consists of a heterogeneous population, making management for these patients complex.Surgery has long been the preferred local treatment for patients with resectable disease.For select patients, multimodality therapy involving systemic and radiation therapies in addition to surgery improves treatment outcomes compared to surgery alone.For patients with unresectable disease, concurrent chemoradiation is the preferred treatment.More recently, research into different chemotherapy agents, targeted therapies, radiation fractionation schedules, intensity-modulated radiotherapy, and proton therapy have shown promise to improve treatment outcomes and quality of life.The array of treatment approaches for locally advanced NSCLC is large and constantly evolving.An updated review of past and current literature for the roles of surgery, chemotherapeutic agents, radiation therapy, and targeted therapy for stage Ⅲ NSCLC patients are presented.展开更多
Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent stu...Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.展开更多
Metastatic breast cancer （MBC） is characterized by a combination of tumor growth, proliferation and metastatic progression and is typically managed with palliative intent. The benefit of standard systemic therapies ...Metastatic breast cancer （MBC） is characterized by a combination of tumor growth, proliferation and metastatic progression and is typically managed with palliative intent. The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies. The detection, enumeration and molecular analysis of circulating tumor cells （CTCs） provide an intriguing opportunity to advance this knowledge. CTCs enumerated by the Food and Drugs Administration-cleared CellSearchTM system are an independent prognostic factor of progression- free survival （PFS） and overall survival （OS） in MBC patients. Several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count _〉5 in 7.5 mL of blood. Therefore, the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests. During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial- mesenchymal transition （EMT）. This important phenomenon is associated with down regulation of epithelial marker （e.g., EpCAM） with potential limitations in the applicability of current CTCs enrichment methods. Such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs. Theoretically, the phenotypic analysis of CTCs can represent a ＂liquid＂ biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.展开更多
Angiogenesis is a very complex physiological process, which involves multiple pathways that are dependent on the homeostatic balance between the growth factors （stimulators and inhibitors）. This tightly controlled p...Angiogenesis is a very complex physiological process, which involves multiple pathways that are dependent on the homeostatic balance between the growth factors （stimulators and inhibitors）. This tightly controlled process is stimulated by angiogenic factors, which are present within the tumor and surrounding tumor-associated stromal cells. The dependence of tumor propagation, invasion and metastasis on angiogenesis makes the inhibitors of new blood vessel formation attractive drugs for treating the malignancies. Angiogenesis can be disrupted by several distinct mechanisms： by inhibiting endothelial cells, by interrupting the signaling pathways or by inhibiting other activators of angiogenesis. This strategy has shown therapeutic benefit in several types of solid tumors, leading to Food and Drug Administration （FDA） approval of anti-angiogenic agents in the treatment of kidney, non-small cell lung, colon and brain cancers. Although no angiogenesis inhibitors have been approved for patients with metastatic prostate cancer, therapies that target new blood vessel formation are still an emerging and Dromising area of prostate cancer research.展开更多
Through advances in technology,the genetic basis of cancer has been investigated at the genomic level,and many fundamental questions have begun to be addressed.Among several key unresolved questions in cancer biology,...Through advances in technology,the genetic basis of cancer has been investigated at the genomic level,and many fundamental questions have begun to be addressed.Among several key unresolved questions in cancer biology,the molecular basis for the link between nuclear deformation and malignancy has not been determined.Another hallmark of human cancer is aneuploidy;however,the causes and consequences of aneuploidy are unanswered and are hotly contested topics.We found that nuclear lamina proteins lamin A/C are absent in a significant fraction(38%) of human breast cancer tissues.Even in lamin A/C-positive breast cancer,lamin A/C expression is heterogeneous or aberrant(such as non-nuclear distribution) in the population of tumor cells,as determined by immunohistology and immunofluorescence microscopy.In most breast cancer cell lines,a significant fraction of the lamin A/C-negative population was observed.To determine the consequences of the loss of lamin A/C,we suppressed their expression by shRNA in noncancerous primary breast epithelial cells.Down-regulation of lamin A/C in breast epithelial cells led to morphological deformation,resembling that of cancer cells,as observed by immunofluorescence microscopy.The lamin A/C-suppressed breast epithelial cells developed aneuploidy as determined by both flow cytometry and fluorescence in situ hybridization.We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy.展开更多
Pancreatic adenocarcinoma remains one of the deadliest malignancies affecting the older population.We are experiencing a paradigm shift in the treatment of pancreatic cancer in the era of coronavirus disease 2019(COVI...Pancreatic adenocarcinoma remains one of the deadliest malignancies affecting the older population.We are experiencing a paradigm shift in the treatment of pancreatic cancer in the era of coronavirus disease 2019(COVID-19)pandemic.Utilizing neoadjuvant treatment and further conducting a safe surgery while protecting patients in a controlled environment can improve oncological outcomes.On the other hand,an optimal oncologic procedure performed in a hazardous setting could shorten patient survival if recovery is complicated by COVID-19 infection.We believe that oncological treatment protocols must adapt to this new health threat,and pancreatic cancer is not unique in this regard.Although survival may not be as optimistic as most other malignancies,as caregivers and researchers,we are committed to innovating and reshaping the treatment algorithms to minimize morbidity and maximize survival as caregivers and researchers.展开更多
AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.METHODS: The databases including Pub Med and abstracts presented at the American Society of Clinical Oncology meetin...AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.METHODS: The databases including Pub Med and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials(RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer(CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity.RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before(n = 1088) and after chemotherapy(n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival(P = 0.92) and prostatespecific antigen(PSA) progression-free survival(P = 0.13), but reduced its effect on radiographic-prog-ression-free survival(P = 0.04), objective response rate(P < 0.001), and PSA response rate(P < 0.001). Prior chemotherapy significantly increased the specific risk of fluid retention and edema(P < 0.001) and hypokalemia(P < 0.001), but decreased the risk of all-grade hypertension(P < 0.001) attributable to abiraterone. There was no significant difference of cardiac disorders associated with abiraterone between the two settings(P = 0.58). CONCLUSION: Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC.展开更多
BACKGROUND Literature focused on cancer screening and management is lacking in the transgender population.AIM To action to increase contributions to the scientific literature that drives the creation of cancer screeni...BACKGROUND Literature focused on cancer screening and management is lacking in the transgender population.AIM To action to increase contributions to the scientific literature that drives the creation of cancer screening and management protocols for transgender and gender nonconforming(TGNC)patients.METHODS We performed a systematic search of PubMed on January 5th,2022,with the following terms:“TGNC”,OR“transgender”,OR“gender non-conforming”,OR“gender nonbinary”AND“cancer screening”,AND“breast cancer”,AND“cervical cancer”,AND“uterine cancer”,AND“ovarian cancer”,AND“prostate cancer”,AND“testicular cancer”,AND“surveillance”,AND“follow-up”,AND“management”.70 unique publications were used.The findings are discussed under“Screening”and“Management”categories.RESULTS Screening:Current cancer screening recommendations default to cis-gender protocols.However,long-term genderaffirming hormone therapy and loss to follow-up from the gender-specific specialties contribute to a higher risk for cancer development and possible delayed detection.The only known screening guidelines made specifically for this population are from the American College of Radiology for breast cancer.Management:Prior to undergoing Gender Affirmation Surgery(GAS),discussion should address cancer screening and management in the organs remaining in situ.Cancer treatment in this population requires consideration for chemotherapy,radiation,surgery and/or reconstruction.Modification of hormone therapy is decided on a case-by-case basis.The use of prophylactic vs aesthetic techniques in surgery is still debated.CONCLUSION When assessing transgender individuals for GAS,a discussion on the future oncologic risk of the sex-specific organs remaining in situ is essential.Cancer management in this population requires a multidisciplinary approach while the care should be highly individualized with considerations to social,medical,surgical and gender affirming surgery related specifications.Special considerations have to be made during planning for GAS as surgery will alter the anatomy and may render the organ difficult to sample for screening purposes.A discussion with the patient regarding the oncologic risk of remaining organs is imperative prior to GAS.Other special considerations to screening such as the conscious or unconscious will to unassociated with their remaining organs is also a key point to address.We currently lack high quality studies pertinent to the cancer topic in the gender affirmation literature.Further research is required to ensure more comprehensive and individualized care for this population.展开更多
Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been onl...Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.展开更多
AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC)mice with dextran sodium sulfate(DSS)-induced inflammation.METHODS Inflammation driven colorectal carcinogenesis...AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC)mice with dextran sodium sulfate(DSS)-induced inflammation.METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC)mice by administering DSS in their drinking water.Mice were fed a diet supplemented with plecanatide(0-20 ppm)and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated.Plecanatide-mediated activation of guanylate cyclase-C(GC-C)signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP)by ELISA,protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting.Ki-67,c-myc and cyclin D1 were used as markers of proliferation.Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry,respectively.Uroguanylin(UG)and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR).A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures.RESULTS Oral treatment of Apc^(+/Min-FCCC)mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid,flat and indeterminate dysplasias.This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation.Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6,IL-1 TNF),chemokines(MIP-1,IP-10)and growth factors(GCSF and GMCSF)from colon explants derived from mice with acute DSS-induced inflammation.The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues.Although GC-C expression was not altered appreciably,a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon,potentially due to a reduction in intestinal inflammation and/or neoplasia.Taken together,these results suggest that reductions in endogenous UG,accompanied by dysregulation in GC-C signaling,may be an early event in inflammation-promoted colorectal neoplasia;an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice,demonstrating the utility for developing GC-C agonists as chemopreventive agents.展开更多
Hepatitis B virus(HBV),a major cause of human liver disease worldwide,encodes three envelope proteins needed for the attachment and entry of the virus into susceptible host cells.A second virus,hepatitis delta virus,w...Hepatitis B virus(HBV),a major cause of human liver disease worldwide,encodes three envelope proteins needed for the attachment and entry of the virus into susceptible host cells.A second virus,hepatitis delta virus,which is known to enhance liver disease in HBV infected patients,diverts the same HBV envelope proteins to achieve its own assembly and infection.In the lab,lentiviral vectors based on human immunodeficiency virus type 1 can be assembled using the HBV envelope proteins,and will similarly infect susceptible cells.This article provides a partial review and some personal reflections of how these three viruses infect and of how recipient cells become susceptible,along with some consideration of questions that remain to be answered.展开更多
Recent reports show that many cellular RNAs are processed to form circular species that are relatively abundant and resistant to host nucleases.In some cases,such circles actually bind host microRNAs.Such depletion of...Recent reports show that many cellular RNAs are processed to form circular species that are relatively abundant and resistant to host nucleases.In some cases,such circles actually bind host microRNAs.Such depletion of available microRNAs appears to have biological roles;for instance,in homeostasis and disease.These findings regarding host RNA circles support a speculative reappraisal of the origin and mode of replication of hepatitis delta virus,hepatitis delta virus(HDV),an agent with a small circular RNA genome;specifically,it is proposed that in hepatocytes infected with hepatitis B virus(HBV),some viral RNA species are processed to circular forms,which by a series of chance events lead to an RNA that can be both replicated by host enzymes and assembled,using HBV envelope proteins,to form particles some of which are infectious.Such a model also may provide some new insights into the potential pathogenic potential of HDV infections.In return,new insights into HDV might provide information leading to a better understanding of the roles of the host RNA circles.展开更多
The opioid epidemic continues to be a serious public health concern.Many have pointed to prescription drug misuse as a nidus for patients to become addicted to opioids and as such,urologists and other surgical subspec...The opioid epidemic continues to be a serious public health concern.Many have pointed to prescription drug misuse as a nidus for patients to become addicted to opioids and as such,urologists and other surgical subspecialists must critically define optimal pain management for the various procedures performed within their respective disciplines.Controlling pain following penile prosthesis implantation remains a unique challenge for urologists,given the increased pain patients commonly experience in the postoperative setting.Although most of the existing urological literature focuses on interventions performed in the operating room,there are many studies that examine the role of preoperative adjunctive pain medicine in diminishing postoperative narcotic requirements.There are relatively few studies looking at postoperative strategies for managing pain in prosthetic surgery with follow-up past the immediate hospitalization.This review assess the various strategies employed for managing pain following penile implantation through the lens of the current state of the opioid crisis,thus examining how urologists can responsibly treat pain without contributing to the growing threat of opioid addiction.展开更多
Recently published Medical Physics Practice Guideline 5.a. (MPPG 5.a.) by American Association of Physicists in Medicine (AAPM) sets the minimum requirements for treatment planning system (TPS) dose algorithm commissi...Recently published Medical Physics Practice Guideline 5.a. (MPPG 5.a.) by American Association of Physicists in Medicine (AAPM) sets the minimum requirements for treatment planning system (TPS) dose algorithm commissioning and quality assurance (QA). The guideline recommends some validation tests and tolerances based primarily on published AAPM task group reports and the criteria used by IROC Houston. We performed the commissioning and validation of the dose algorithms for both megavoltage photon and electron beams on three linacs following MPPG 5.a. We designed the validation experiments in an attempt to highlight the evaluation method and tolerance criteria recommended by the guideline. It seems that comparison of dose profiles using in-water scan is an effective technique for basic photon and electron validation. IMRT/VMAT dose calculation is recommended to be tested with some TG-119 and clinical cases, but no consensus of the tolerance exists. Extensive validation tests have provided the better understanding of the accuracy and limitation of a specific dose calculation algorithm. We believe that some tests and evaluation criteria given in the guideline can be further refined.展开更多
AIM To further characterize the structure and nucleic acid binding properties of the 195 amino acid small delta antigen, S-HDAg, a study was made of a truncated form of S-HDAg, comprising amino acids 61-195(?60HDAg), ...AIM To further characterize the structure and nucleic acid binding properties of the 195 amino acid small delta antigen, S-HDAg, a study was made of a truncated form of S-HDAg, comprising amino acids 61-195(?60HDAg), thus lacking the domain considered necessary for dimerization and higher order multimerization.METHODS Circular dichroism, and nuclear magnetic resonance experiments were used to assess the structure of ?60HDAg. Nucleic acid binding properties were investigated by gel retardation assays. RESULTS Results showed that the truncated ?60HDAg protein is intrinsically disordered but compact, whereas the RNA binding domain, comprising residues 94-146, adopts a dynamic helical conformation. We also found that ?60HDAg fails to multimerize but still contains nucleic acid binding activity, indicating that multimerization is not essential for nucleic acid binding. Moreover, in agreement with what has been previously reported for full-length protein, no apparent specificity was found for the truncated protein regarding nucleic acid binding.CONCLUSION Taken together these results allowed concluding that ?60HDAg is intrinsically disordered but compact; ?60HDAg is not a multimer but is still capable of nucleic acid binding albeit without apparent specificity.展开更多
The specimens of this study were obtained from 110 cases of chronic hepatitis,108cirrhosis and 110 primary hepatic carcinoma(PHC).Formalin-fixed and paraffin-embedded seetions were stained by ABC method forHBxAg,and b...The specimens of this study were obtained from 110 cases of chronic hepatitis,108cirrhosis and 110 primary hepatic carcinoma(PHC).Formalin-fixed and paraffin-embedded seetions were stained by ABC method forHBxAg,and by PAP method for HRsAg and HBcAgOf the 110 cases of chronic hepatitis,72(65.5％)were positive HBxAg in the liver cells,66(60％)were postitive in HBsAg and 35(31.8％)in HBcAg.Among the 108 eases of drrhosis,84(77.8％)revealed to be HBxAg positive in the liver cells,73(67.6％)were demonstrated to beHBsAg-positive and 18(16.7％)were shown to be HBcAg-positive.Among the 110 eases of pri-mary hepatic carcinoma,64(58.2％)showed HBxAg-positive reaction in cancerous tissues.Therates of positive HRsAg and HBcAg in tumor tissues were 15.5％ and 10.9％,respectively.Six-ty-three(78.8％)of 80 cases of the non-cancerous hepatic tissues displayed HBxAg positivenessand the rates of positive HRsAg and HBcAg in the non-tumor tissues were 47(58.8％)and 21(2.6.3％),respectively.The above-mentioned results sugared that the detection rote of HBxAg inchronic hepatitis,cirrhosis and PHC was higher than that of HBsAg and HBcAg.This studydemonstrates a dose relationship between chronic hepatitis,cirrhosis,PHC and chronic persistentinfection of hepatitis B virus(HBV).Persistent chronic HBV infection plays an important role inthe pathogenesis of chronic hepatitis, cirrhosis and PHC.It is possible that the detection ofHBxAg with anti-HBx could be an additional new diagnostic marker for HBV infection.Howev-er,the role of HBxAg in the pathogenesis of chronic liver diseases needs to be furtherinvestigated.展开更多
The specimens of 135 cases of primary hepatic carcinoma were obtained from the Pathological Laboratory of the First Affiliated Hospital of the Fourth Military Medical University, Xi' an, PRC. Ten percent formalin-...The specimens of 135 cases of primary hepatic carcinoma were obtained from the Pathological Laboratory of the First Affiliated Hospital of the Fourth Military Medical University, Xi' an, PRC. Ten percent formalin-fixed and paraffin- embedded sections were stained by HE and by ABC and PAP immunohistochemical methods. Positive rates of pre- S1 and pre- S2 antigens in cancerous tissue were 22. 2% and 20. 0%, respectively, while those in surrounding hepatic tissue were 60.6% and 59.6%, separately. The pre- S1 and pre- S2 antigens were found to coexist In 16. 3% of cancerous tissue and in 55. 6% of surrounding hepatic tissue. In all the 135 cases of hepatic carcinoma, the cancerous tissue showed positive HBsAg in 16. 3%, HBxAg in 55. 6% and HBcAg in 8. 9%; in the surrounding hepatic tissue, positive HBsAg was 59.6%, HBxAg 78.8% and HBcAg 24.2%. The results of this study suggestes that positive rates of pre- S1 and pre-S2 antigens in cancerous tissue were slightly higher than that of HBsAg, but markedly lower than that of HBxAg. The positive rate of pre-S1 and pre- S2 antigens in surrounding hepatic tissue was nearly the same as HBsAg, but slightly lower than that of HBxAg. Antigens of pre-S1 and pre-S2 are the new markers of HBV infection. The same as other antigens, they may play an important role in the development of hepatic carcinoma. The mechanism of their effect will be further investigated,展开更多
文摘Lung cancer is the leading cause of cancer death worldwide.Majority of newly diagnosed lung cancers are non-small cell lung cancer(NSCLC), of which up to half are considered locally advanced at the time of diagnosis.Patients with locally advanced stage Ⅲ NSCLC consists of a heterogeneous population, making management for these patients complex.Surgery has long been the preferred local treatment for patients with resectable disease.For select patients, multimodality therapy involving systemic and radiation therapies in addition to surgery improves treatment outcomes compared to surgery alone.For patients with unresectable disease, concurrent chemoradiation is the preferred treatment.More recently, research into different chemotherapy agents, targeted therapies, radiation fractionation schedules, intensity-modulated radiotherapy, and proton therapy have shown promise to improve treatment outcomes and quality of life.The array of treatment approaches for locally advanced NSCLC is large and constantly evolving.An updated review of past and current literature for the roles of surgery, chemotherapeutic agents, radiation therapy, and targeted therapy for stage Ⅲ NSCLC patients are presented.
基金supported in part by a grant from the National Cancer Institute,USA (No. R01CA085560)
文摘Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.
文摘Metastatic breast cancer （MBC） is characterized by a combination of tumor growth, proliferation and metastatic progression and is typically managed with palliative intent. The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies. The detection, enumeration and molecular analysis of circulating tumor cells （CTCs） provide an intriguing opportunity to advance this knowledge. CTCs enumerated by the Food and Drugs Administration-cleared CellSearchTM system are an independent prognostic factor of progression- free survival （PFS） and overall survival （OS） in MBC patients. Several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count _〉5 in 7.5 mL of blood. Therefore, the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests. During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial- mesenchymal transition （EMT）. This important phenomenon is associated with down regulation of epithelial marker （e.g., EpCAM） with potential limitations in the applicability of current CTCs enrichment methods. Such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs. Theoretically, the phenotypic analysis of CTCs can represent a ＂liquid＂ biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.
文摘Angiogenesis is a very complex physiological process, which involves multiple pathways that are dependent on the homeostatic balance between the growth factors （stimulators and inhibitors）. This tightly controlled process is stimulated by angiogenic factors, which are present within the tumor and surrounding tumor-associated stromal cells. The dependence of tumor propagation, invasion and metastasis on angiogenesis makes the inhibitors of new blood vessel formation attractive drugs for treating the malignancies. Angiogenesis can be disrupted by several distinct mechanisms： by inhibiting endothelial cells, by interrupting the signaling pathways or by inhibiting other activators of angiogenesis. This strategy has shown therapeutic benefit in several types of solid tumors, leading to Food and Drug Administration （FDA） approval of anti-angiogenic agents in the treatment of kidney, non-small cell lung, colon and brain cancers. Although no angiogenesis inhibitors have been approved for patients with metastatic prostate cancer, therapies that target new blood vessel formation are still an emerging and Dromising area of prostate cancer research.
基金supported by funds from concept awards BC097189 and BC076832 from Department of Defense(USA)Grants R01CA095071,R01CA099471,and CA79716to Xiang-Xi Xu from NCI
文摘Through advances in technology,the genetic basis of cancer has been investigated at the genomic level,and many fundamental questions have begun to be addressed.Among several key unresolved questions in cancer biology,the molecular basis for the link between nuclear deformation and malignancy has not been determined.Another hallmark of human cancer is aneuploidy;however,the causes and consequences of aneuploidy are unanswered and are hotly contested topics.We found that nuclear lamina proteins lamin A/C are absent in a significant fraction(38%) of human breast cancer tissues.Even in lamin A/C-positive breast cancer,lamin A/C expression is heterogeneous or aberrant(such as non-nuclear distribution) in the population of tumor cells,as determined by immunohistology and immunofluorescence microscopy.In most breast cancer cell lines,a significant fraction of the lamin A/C-negative population was observed.To determine the consequences of the loss of lamin A/C,we suppressed their expression by shRNA in noncancerous primary breast epithelial cells.Down-regulation of lamin A/C in breast epithelial cells led to morphological deformation,resembling that of cancer cells,as observed by immunofluorescence microscopy.The lamin A/C-suppressed breast epithelial cells developed aneuploidy as determined by both flow cytometry and fluorescence in situ hybridization.We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy.
文摘Pancreatic adenocarcinoma remains one of the deadliest malignancies affecting the older population.We are experiencing a paradigm shift in the treatment of pancreatic cancer in the era of coronavirus disease 2019(COVID-19)pandemic.Utilizing neoadjuvant treatment and further conducting a safe surgery while protecting patients in a controlled environment can improve oncological outcomes.On the other hand,an optimal oncologic procedure performed in a hazardous setting could shorten patient survival if recovery is complicated by COVID-19 infection.We believe that oncological treatment protocols must adapt to this new health threat,and pancreatic cancer is not unique in this regard.Although survival may not be as optimistic as most other malignancies,as caregivers and researchers,we are committed to innovating and reshaping the treatment algorithms to minimize morbidity and maximize survival as caregivers and researchers.
文摘AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.METHODS: The databases including Pub Med and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials(RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer(CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity.RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before(n = 1088) and after chemotherapy(n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival(P = 0.92) and prostatespecific antigen(PSA) progression-free survival(P = 0.13), but reduced its effect on radiographic-prog-ression-free survival(P = 0.04), objective response rate(P < 0.001), and PSA response rate(P < 0.001). Prior chemotherapy significantly increased the specific risk of fluid retention and edema(P < 0.001) and hypokalemia(P < 0.001), but decreased the risk of all-grade hypertension(P < 0.001) attributable to abiraterone. There was no significant difference of cardiac disorders associated with abiraterone between the two settings(P = 0.58). CONCLUSION: Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC.
文摘BACKGROUND Literature focused on cancer screening and management is lacking in the transgender population.AIM To action to increase contributions to the scientific literature that drives the creation of cancer screening and management protocols for transgender and gender nonconforming(TGNC)patients.METHODS We performed a systematic search of PubMed on January 5th,2022,with the following terms:“TGNC”,OR“transgender”,OR“gender non-conforming”,OR“gender nonbinary”AND“cancer screening”,AND“breast cancer”,AND“cervical cancer”,AND“uterine cancer”,AND“ovarian cancer”,AND“prostate cancer”,AND“testicular cancer”,AND“surveillance”,AND“follow-up”,AND“management”.70 unique publications were used.The findings are discussed under“Screening”and“Management”categories.RESULTS Screening:Current cancer screening recommendations default to cis-gender protocols.However,long-term genderaffirming hormone therapy and loss to follow-up from the gender-specific specialties contribute to a higher risk for cancer development and possible delayed detection.The only known screening guidelines made specifically for this population are from the American College of Radiology for breast cancer.Management:Prior to undergoing Gender Affirmation Surgery(GAS),discussion should address cancer screening and management in the organs remaining in situ.Cancer treatment in this population requires consideration for chemotherapy,radiation,surgery and/or reconstruction.Modification of hormone therapy is decided on a case-by-case basis.The use of prophylactic vs aesthetic techniques in surgery is still debated.CONCLUSION When assessing transgender individuals for GAS,a discussion on the future oncologic risk of the sex-specific organs remaining in situ is essential.Cancer management in this population requires a multidisciplinary approach while the care should be highly individualized with considerations to social,medical,surgical and gender affirming surgery related specifications.Special considerations have to be made during planning for GAS as surgery will alter the anatomy and may render the organ difficult to sample for screening purposes.A discussion with the patient regarding the oncologic risk of remaining organs is imperative prior to GAS.Other special considerations to screening such as the conscious or unconscious will to unassociated with their remaining organs is also a key point to address.We currently lack high quality studies pertinent to the cancer topic in the gender affirmation literature.Further research is required to ensure more comprehensive and individualized care for this population.
基金supported by R01 grants CA-083859 and CA-100226 (K.S.C.)training grant CA009035-32 (A.K.P.)+1 种基金partially by Centers of Research Excellence grant CA06927 (FCCC) from the National Institutes of Healthsupported in part by an appropriation from the Commonwealth of Pennsylvania
文摘自然杀伤(natural killer,NK)细胞是先天性免疫效应细胞,约占人外周血淋巴细胞总数的10%-15%,主要参与免疫监视,以消除转化细胞和病毒感染细胞。NK细胞最初被界定是由于它们具有自发消除少数主要组织相容性复合物I类(major histocompatibility class I,MHC-I)自身分子表达缺乏细胞的能力,即常说的"丢失自我"识别能力。NK细胞表面表达的MHC-I特异性抑制性受体,可使NK细胞对表达MHC-I的正常细胞耐受,此为丢失自我识别能力的分子基础。由于缺乏抑制性受体的配体,表面MHC-I表达下调的肿瘤细胞和病毒感染细胞易受NK细胞攻击。杀伤细胞免疫球蛋白样受体(KIR;CD158)组成MHC-I结合受体家族,对调节人NK细胞和部分T细胞的活化阈值起重要作用。KIR多样性使NK细胞具有多种功能,在此我们将综述多个水平上的KIR多样性,并诠释KIR多样性是如何影响各种疾病(包括癌症)的易感性的。我们将进一步阐述通过针对KIR进行癌症治疗的策略:利用KIR/MHC-I配体的错配以强化造血干细胞移植的效果,以及通过阻滞KIR以增强对肿瘤细胞的杀伤力。
文摘Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.
基金Supported by National Cancer Institute(CA133689 to Kunwar Shailubhai,CA006927 to Fox Chase Cancer Center)an appropriation from the Commonwealth of Pennsylvania(Fox Chase Cancer Center)
文摘AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC)mice with dextran sodium sulfate(DSS)-induced inflammation.METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC)mice by administering DSS in their drinking water.Mice were fed a diet supplemented with plecanatide(0-20 ppm)and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated.Plecanatide-mediated activation of guanylate cyclase-C(GC-C)signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP)by ELISA,protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting.Ki-67,c-myc and cyclin D1 were used as markers of proliferation.Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry,respectively.Uroguanylin(UG)and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR).A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures.RESULTS Oral treatment of Apc^(+/Min-FCCC)mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid,flat and indeterminate dysplasias.This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation.Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6,IL-1 TNF),chemokines(MIP-1,IP-10)and growth factors(GCSF and GMCSF)from colon explants derived from mice with acute DSS-induced inflammation.The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues.Although GC-C expression was not altered appreciably,a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon,potentially due to a reduction in intestinal inflammation and/or neoplasia.Taken together,these results suggest that reductions in endogenous UG,accompanied by dysregulation in GC-C signaling,may be an early event in inflammation-promoted colorectal neoplasia;an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice,demonstrating the utility for developing GC-C agonists as chemopreventive agents.
文摘Hepatitis B virus(HBV),a major cause of human liver disease worldwide,encodes three envelope proteins needed for the attachment and entry of the virus into susceptible host cells.A second virus,hepatitis delta virus,which is known to enhance liver disease in HBV infected patients,diverts the same HBV envelope proteins to achieve its own assembly and infection.In the lab,lentiviral vectors based on human immunodeficiency virus type 1 can be assembled using the HBV envelope proteins,and will similarly infect susceptible cells.This article provides a partial review and some personal reflections of how these three viruses infect and of how recipient cells become susceptible,along with some consideration of questions that remain to be answered.
文摘Recent reports show that many cellular RNAs are processed to form circular species that are relatively abundant and resistant to host nucleases.In some cases,such circles actually bind host microRNAs.Such depletion of available microRNAs appears to have biological roles;for instance,in homeostasis and disease.These findings regarding host RNA circles support a speculative reappraisal of the origin and mode of replication of hepatitis delta virus,hepatitis delta virus(HDV),an agent with a small circular RNA genome;specifically,it is proposed that in hepatocytes infected with hepatitis B virus(HBV),some viral RNA species are processed to circular forms,which by a series of chance events lead to an RNA that can be both replicated by host enzymes and assembled,using HBV envelope proteins,to form particles some of which are infectious.Such a model also may provide some new insights into the potential pathogenic potential of HDV infections.In return,new insights into HDV might provide information leading to a better understanding of the roles of the host RNA circles.
文摘The opioid epidemic continues to be a serious public health concern.Many have pointed to prescription drug misuse as a nidus for patients to become addicted to opioids and as such,urologists and other surgical subspecialists must critically define optimal pain management for the various procedures performed within their respective disciplines.Controlling pain following penile prosthesis implantation remains a unique challenge for urologists,given the increased pain patients commonly experience in the postoperative setting.Although most of the existing urological literature focuses on interventions performed in the operating room,there are many studies that examine the role of preoperative adjunctive pain medicine in diminishing postoperative narcotic requirements.There are relatively few studies looking at postoperative strategies for managing pain in prosthetic surgery with follow-up past the immediate hospitalization.This review assess the various strategies employed for managing pain following penile implantation through the lens of the current state of the opioid crisis,thus examining how urologists can responsibly treat pain without contributing to the growing threat of opioid addiction.
文摘Recently published Medical Physics Practice Guideline 5.a. (MPPG 5.a.) by American Association of Physicists in Medicine (AAPM) sets the minimum requirements for treatment planning system (TPS) dose algorithm commissioning and quality assurance (QA). The guideline recommends some validation tests and tolerances based primarily on published AAPM task group reports and the criteria used by IROC Houston. We performed the commissioning and validation of the dose algorithms for both megavoltage photon and electron beams on three linacs following MPPG 5.a. We designed the validation experiments in an attempt to highlight the evaluation method and tolerance criteria recommended by the guideline. It seems that comparison of dose profiles using in-water scan is an effective technique for basic photon and electron validation. IMRT/VMAT dose calculation is recommended to be tested with some TG-119 and clinical cases, but no consensus of the tolerance exists. Extensive validation tests have provided the better understanding of the accuracy and limitation of a specific dose calculation algorithm. We believe that some tests and evaluation criteria given in the guideline can be further refined.
基金Supported by Fundação para a Ciência e Tecnologia,FCT,to GHTM-UID/Multi/04413/2013Carolina Alves and Ana Casaca were recipients of FCT PhD grantsJoão Paulo Tavanez is a recipient of a FCT post-doctoral fellowship SFRH/BPD/87494/2012.
文摘AIM To further characterize the structure and nucleic acid binding properties of the 195 amino acid small delta antigen, S-HDAg, a study was made of a truncated form of S-HDAg, comprising amino acids 61-195(?60HDAg), thus lacking the domain considered necessary for dimerization and higher order multimerization.METHODS Circular dichroism, and nuclear magnetic resonance experiments were used to assess the structure of ?60HDAg. Nucleic acid binding properties were investigated by gel retardation assays. RESULTS Results showed that the truncated ?60HDAg protein is intrinsically disordered but compact, whereas the RNA binding domain, comprising residues 94-146, adopts a dynamic helical conformation. We also found that ?60HDAg fails to multimerize but still contains nucleic acid binding activity, indicating that multimerization is not essential for nucleic acid binding. Moreover, in agreement with what has been previously reported for full-length protein, no apparent specificity was found for the truncated protein regarding nucleic acid binding.CONCLUSION Taken together these results allowed concluding that ?60HDAg is intrinsically disordered but compact; ?60HDAg is not a multimer but is still capable of nucleic acid binding albeit without apparent specificity.
文摘The specimens of this study were obtained from 110 cases of chronic hepatitis,108cirrhosis and 110 primary hepatic carcinoma(PHC).Formalin-fixed and paraffin-embedded seetions were stained by ABC method forHBxAg,and by PAP method for HRsAg and HBcAgOf the 110 cases of chronic hepatitis,72(65.5％)were positive HBxAg in the liver cells,66(60％)were postitive in HBsAg and 35(31.8％)in HBcAg.Among the 108 eases of drrhosis,84(77.8％)revealed to be HBxAg positive in the liver cells,73(67.6％)were demonstrated to beHBsAg-positive and 18(16.7％)were shown to be HBcAg-positive.Among the 110 eases of pri-mary hepatic carcinoma,64(58.2％)showed HBxAg-positive reaction in cancerous tissues.Therates of positive HRsAg and HBcAg in tumor tissues were 15.5％ and 10.9％,respectively.Six-ty-three(78.8％)of 80 cases of the non-cancerous hepatic tissues displayed HBxAg positivenessand the rates of positive HRsAg and HBcAg in the non-tumor tissues were 47(58.8％)and 21(2.6.3％),respectively.The above-mentioned results sugared that the detection rote of HBxAg inchronic hepatitis,cirrhosis and PHC was higher than that of HBsAg and HBcAg.This studydemonstrates a dose relationship between chronic hepatitis,cirrhosis,PHC and chronic persistentinfection of hepatitis B virus(HBV).Persistent chronic HBV infection plays an important role inthe pathogenesis of chronic hepatitis, cirrhosis and PHC.It is possible that the detection ofHBxAg with anti-HBx could be an additional new diagnostic marker for HBV infection.Howev-er,the role of HBxAg in the pathogenesis of chronic liver diseases needs to be furtherinvestigated.
文摘The specimens of 135 cases of primary hepatic carcinoma were obtained from the Pathological Laboratory of the First Affiliated Hospital of the Fourth Military Medical University, Xi' an, PRC. Ten percent formalin-fixed and paraffin- embedded sections were stained by HE and by ABC and PAP immunohistochemical methods. Positive rates of pre- S1 and pre- S2 antigens in cancerous tissue were 22. 2% and 20. 0%, respectively, while those in surrounding hepatic tissue were 60.6% and 59.6%, separately. The pre- S1 and pre- S2 antigens were found to coexist In 16. 3% of cancerous tissue and in 55. 6% of surrounding hepatic tissue. In all the 135 cases of hepatic carcinoma, the cancerous tissue showed positive HBsAg in 16. 3%, HBxAg in 55. 6% and HBcAg in 8. 9%; in the surrounding hepatic tissue, positive HBsAg was 59.6%, HBxAg 78.8% and HBcAg 24.2%. The results of this study suggestes that positive rates of pre- S1 and pre-S2 antigens in cancerous tissue were slightly higher than that of HBsAg, but markedly lower than that of HBxAg. The positive rate of pre-S1 and pre- S2 antigens in surrounding hepatic tissue was nearly the same as HBsAg, but slightly lower than that of HBxAg. Antigens of pre-S1 and pre-S2 are the new markers of HBV infection. The same as other antigens, they may play an important role in the development of hepatic carcinoma. The mechanism of their effect will be further investigated,
