Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the im...Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.展开更多
Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonf...Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K(HML6) and HERV-K(HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K(HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.展开更多
Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from A...Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.展开更多
Many hematopoietic malignancies have oncogenic gene fusions, like BCR-ABL, in their tumor-initiating cells. This implicates the product of the fusion as a powerful cancer-initiating event. In human prostate cancers, d...Many hematopoietic malignancies have oncogenic gene fusions, like BCR-ABL, in their tumor-initiating cells. This implicates the product of the fusion as a powerful cancer-initiating event. In human prostate cancers, despite the detection of numerous similar fusions,展开更多
Background:The epidemiological profiles of gastrointestinal(GI)cancers vary across countries and over time,largely reflecting variations in risk factors and screening practices.We aimed to provide an overview of the c...Background:The epidemiological profiles of gastrointestinal(GI)cancers vary across countries and over time,largely reflecting variations in risk factors and screening practices.We aimed to provide an overview of the current global burden of the five major types of GI cancers and conduct an updated evaluation of the long-term trends of GI cancers.Methods:The updated numbers of new cases and deaths,and age-standardized rates(ASR),of the five GI cancers for 185 countries were sourced from the GLOBOCAN 2022,and presented by cancer site,continent,and human development index(HDI).For 43 countries,annual incidence and mortality data were obtained from the Cancer Incidence in Five Continents Plus and World Health Organization mortality databases,supplemented by the mortality data from the Disease Surveillance Points system for China.We compared the longterm trends of ASRs across countries since 1980,and estimated average annual percent changes(AAPCs)for the recent period 2003-2017.Results:In 2022,there were 4,783,391 new cases and 3,235,719 deaths from the five GI cancers,accounting for 23.9%and 33.2%of all new cancer cases and deaths worldwide,respectively.Cancers of oesophagus,stomach,and liver were more common in Asian and high HDI countries,and colorectal and pancreatic cancer in western and very high HDI countries.Downward trends were observed in almost all countries for gastric cancer and most countries for oesophageal cancer.For colorectal cancer,the most favorable and unfavorable trends were found in 10 and 19 countries respectively.The largest decreases in liver cancer burden were mainly in eastern and southeastern Asia,while increases were seen in North America,Oceania,and Northern Europe,with AAPCs of 3%∼7%for incidence and 2%∼9%for mortality during 2003-2017.Half of the included countries showed increases in pancreatic cancer burden,with the largest AAPCs in Cyprus,Thailand,India,Türkiye,France,and Belarus for incidence,and Türkiye,Thailand,and China for mortality.Conclusions:Deviating patterns were found for GI cancers worldwide.Multisetting studies might provide insights into the underlying etiologies of these cancers,and identify areas where urgent cancer control strategies are needed.展开更多
The 2024 updates of the Chinese Society of Clinical Oncology(CSCO)Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China,highlighting the latest adva...The 2024 updates of the Chinese Society of Clinical Oncology(CSCO)Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China,highlighting the latest advancements in evidence-based medicine,healthcare resource access,and precision medicine in oncology.These updates address disparities in epidemiological trends,clinicopathological characteristics,tumor biology,treatment approaches,and drug selection for colorectal cancer patients across diverse regions and backgrounds.Key revisions include adjustments to evidence levels for intensive treatment strategies,updates to regimens for deficient mismatch repair(dMMR)/microsatellite instability-high(MSI-H)patients,proficient mismatch repair(pMMR)/microsatellite stability(MSS)patients who have failed standard therapies,and rectal cancer patients with low recurrence risk.Additionally,recommendations for digital rectal examination and DNA polymerase epsilon(POLE)/DNA polymerase delta 1(POLD1)gene mutation testing have been strengthened.The 2024CSCOGuidelines are based on both Chinese and international clinical research,aswell as expert consensus,ensuring their relevance and applicability in clinical practice,while maintaining a commitment to scientific rigor,impartiality,and timely updates.展开更多
During the last years increasing evidence implies that human cytomegalovirus(CMV) can be attributed to human malignancies arising from numerous tissues. In this perspective, we will review and discuss the potential me...During the last years increasing evidence implies that human cytomegalovirus(CMV) can be attributed to human malignancies arising from numerous tissues. In this perspective, we will review and discuss the potential mechanisms through which CMV infection may contribute to brain tumors by affecting tumor cell initiation, progression and metastasis formation. Recent evidence also suggests that anti-CMV treatment results in impaired tumor growth of CMV positive xenografts in animal models and potentially increased survival in CMV positive glioblastoma patients. Based on these observations and the high tumor promoting capacity of this virus, the classical and novel antiviral therapies against CMV should be revisited as they may represent a great promise for halting tumor progression and lower cancer deaths.展开更多
Objective: To determine the cytotoxicity, reduction in nitric oxide production and antioxidative activity of the aqueous leaf extract from Tithonia diversifolia(T. diversifolia) in an in vitro model.Methods: Leaves of...Objective: To determine the cytotoxicity, reduction in nitric oxide production and antioxidative activity of the aqueous leaf extract from Tithonia diversifolia(T. diversifolia) in an in vitro model.Methods: Leaves of T. diversifolia were collected from natural habitats and extracted with distilled water using the decoction method. The cytotoxic effect of the extract in terms of cell viability was determined using RAW264.7 cells and human peripheral blood mononuclear cells(PBMCs) via the mitochondrial respiration method using the MTT reagent. The effect of the extract on lipopolysaccharide(LPS)-induced nitric oxide production in RAW264.7 cells was measured using the Griess reagent. The chemical antioxidant was evaluated by ABTS- and DPPH-radical scavenging assays.Results: The half-maximal cytotoxic concentration values were 145.87 mg/m L and73.67 mg/m L for human PBMCs and RAW264.7 cells, respectively. In the presence of phytohemagglutinin-M, the IC_(50) on PBMCs proliferation was 4.42 mg/m L. The noncytotoxic range of the extracts inhibited LPS-induced nitrite production in RAW264.7 cells with an IC_(50) value of 11.63 mg/m L. To determine the anti-oxidative properties, the N-acetyl cysteine equivalent antioxidant capacity of the extract was(32.62 ± 1.87) and(20.99 ± 2.79)mg N-acetyl cysteine/g extract, respectively determined by the ABTS-radical and DPPHradical assay. However, the extract did not confer death protection in a hydrogen peroxideinduced RAW264.7 co-culturing model.Conclusions: Our study demonstrated the immunomodulation caused by the aqueous leaf extract of T. diversifolia, resulting from the inhibition of phytohemagglutinin-Minduced PBMCs proliferation and LPS-induced nitric oxide production in RAW264.7macrophages. Although the anti-oxidative activity was presented in the chemical-based anti-oxidant assay, the extract cannot protect cell death from stress conditions.展开更多
Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific mol...Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.展开更多
Sunlight is a known skin carcinogen. Skin cancer is the most common form of cancer in humans, and typically affects sun-exposed parts of the body. Sunny Australia and New Zealand have the highest incidence of skin can...Sunlight is a known skin carcinogen. Skin cancer is the most common form of cancer in humans, and typically affects sun-exposed parts of the body. Sunny Australia and New Zealand have the highest incidence of skin cancer globally. Clothing provides a protective barrier that reduces the amount of ultraviolet radiation (UVR) reaching the skin. Australia pioneered the development of a relative ranking of the sun-protective capabilities of clothing based on the transmission of UVR through fabric. Standardized Ultraviolet Protection Factor (UPF) measurement procedures and associated labeling specifications are documented in the Australian and New Zealand Standard, AS/NZS 4399:1996. The standard was intended to enable consumers to make informed choices. Since its introduction, this standard has been adopted almost universally by the textile industry, and is still in use almost two decades on, with plans to revise it only commencing recently. However, AS/NZS 4399:1996 does not consider garment design, particularly in relation to body surface coverage. Although swim-shirts have grown in popularity in Australia since the late 1990s, particularly among children, clothing remains under-utilized as a form of sun-protection in contemporary society. Skin cancer prevention campaigns should emphasize the sun-protective benefits of clothing and collaboration with the fashion industry is urgently needed to improve the aesthetic appeal, comfort, durability and affordability of sun-protective clothing to increase its popularity in skin cancer prone populations. In light of recent evidence showing that high UPF clothing which covers more of the body surface reduces pigmented mole development in children (major risk factor for melanoma), the rating system for sun-protective clothing should incorporate body surface covered as well as the UPF of the fabric. We discuss progress towards developing a protocol for measuring the extent of coverage of sun-protective garments. Once fully evaluated and refined, the testing protocol developed from this research may influence future revisions of international standards for evaluating and classifying sun-protective clothing.展开更多
Sympathetic neuronal differentiation is associated with favorable prognosis of neuroblastoma （NB）, the most common extra-cranial solid tumor of early childhood. Differentiation agents have proved useful in clinical ...Sympathetic neuronal differentiation is associated with favorable prognosis of neuroblastoma （NB）, the most common extra-cranial solid tumor of early childhood. Differentiation agents have proved useful in clinical protocols of NB treatment, but using them as a sole treatment is not sufficient to induce tumor elimination in patients. Therefore, complementary approaches, such as immunotherapy, are warranted. Here we demonstrate that differentiation of NB cell lines and ex vivo isolated tumor cells in response to physiological or pharmacological stimuli is associated with acquisition of increased antigenicity. This manifests as increased expression of surface major histocompatibility class I complexes and ICAM-1 molecules and translates into increased sensitivity of NB cells to lysis by cytotoxic T lymphocytes （CTLs） and natural killer （NK） cells. The latter is paralleled by enhanced ability of differentiated cells to form immune conjugates and bind increased amounts of granzyme B to the cell surface. We demonstrate, for the first time, that, regardless of the stimulus applied, the differentiation state in NBs is associated with increased tumor antigenicity that enables more efficient elimination of tumor cells by cytotoxic lymphocytes and paves the way for combined application of differentiation-inducing agents and immunotherapy as an auxiliary approach in NB patients.展开更多
Currently,lymph node metastases(LNM)are seen as the gateway to distant metastases in CRC and play a crucial role in the Tumor Node Metastasis(TNM)staging system[1,2].Tumor deposits(TD)have been identified as another h...Currently,lymph node metastases(LNM)are seen as the gateway to distant metastases in CRC and play a crucial role in the Tumor Node Metastasis(TNM)staging system[1,2].Tumor deposits(TD)have been identified as another histological feature with a strong prognostic impact but are currently only deemed clinically relevant in the absence of LNM[2,3].TD are clusters of tumor cells in the fat surrounding the bowel and are often associated with nerves,vessels and lymphatic tissue,giving the cancer cells access to multiple routes of spread[4].展开更多
Genetic alterations to serine-threonine kinase 11(STK11)have been implicated in Peutz-Jeghers syndrome and tumorigenesis.Further exploration of the context-specific roles of liver kinase B1(LKB1;encoded by STK11)obser...Genetic alterations to serine-threonine kinase 11(STK11)have been implicated in Peutz-Jeghers syndrome and tumorigenesis.Further exploration of the context-specific roles of liver kinase B1(LKB1;encoded by STK11)observed that it regulates AMP-activated protein ki-nase(AMPK)and AMPK-related kinases.Given that both migration and proliferation are enhanced with the loss of LKB1 activity combined with the prevalence of STK11 genetic alter-ations in cancer biopsies,LKB1 was markedas a tumor suppressor.However,the roleof LKB1 in tumorigenesis is paradoxical as LKB1 activates autophagy and reactive oxygen species scav-enging while dampening anoikis,which contribute to cancer cell survival.Due to the pro-tumor-igenic properties of LKB1,targeting LKB1 pathways is now relevant for cancer treatment.With the recent successes of targeting LKB1 signaling in research and clinical settings,and enhanced cytotoxicity of chemical compounds in LKB1-deficient tumors,there is now a need for LKB1 in-hibitors.However,validating LKB1 inhibitors is challenging as LKB1 adaptor proteins,nucleocy-toplasmic shuttling,and splice variants all manipulate LKB1 activity.Furthermore,STE-20-related kinase adaptor protein(STRAD)and mouse protein 25 dictate LKB1 cellular localization and kinase activity.For these reasons,prior to assessing the efficacy and potency of pharmaco-logical candidates,the functional status of LKB1 needs to be defined.Therefore,to improve the understanding of LKB1 in physiology and oncology,this review highlights the role of LKB1 in tumorigenesis and addresses the therapeutic relevancy of LKB1 inhibitors..展开更多
Pancreatic ductal adenocarcinoma(PDAC)remains one of medicine’s most urgent areas of unmet need.With 5-year survival rates of∼11%,PDAC is set to become the second leading cause of cancer related deaths by 2040[1].Th...Pancreatic ductal adenocarcinoma(PDAC)remains one of medicine’s most urgent areas of unmet need.With 5-year survival rates of∼11%,PDAC is set to become the second leading cause of cancer related deaths by 2040[1].The complex tumour microenvironment(TME)in PDAC,responsible for poor prognosis,is comprised of extracellular matrix(ECM)proteins and multiple cell types;with pancreatic stellate cells(PSCs),which become activated cancer associated fibroblasts(CAFs),being regarded as key orchestrators of the TME.We have demonstrated that treatment with all-trans retinoic acid(ATRA)can render activated PSCs(aPSC)to a quiescent(qPSC)phenotype(shift to G1 phase of cell cycle and other features[2]),resulting in stromal remodelling and thus,influencing cancer cell co-targeting with chemotherapy in patients[3].This has resulted in the use of ATRA along with standard-of-care chemotherapy in the Stromal TARgeting for PAncreatic Cancer(STARPAC)clinical trial,with promising results[4].These clinically relevant[5],exciting potential therapeutic benefits of stromal co-targeting through rendering PSCs quiescent[6],along with predictive inflammation-related biomarkers[7],and increased focus on cellular therapeutics such as NK cells,led us to postulate potential targetable PSC-immune cell interactions which may uncover a comprehensive therapeutic strategy for treating hitherto,incurable PDAC.展开更多
Human immunodeficiency virus type-1 （HIV-1）-specific dendritic cell （DC） vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. W...Human immunodeficiency virus type-1 （HIV-1）-specific dendritic cell （DC） vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. We previously demonstrated that the HIV-1 Gag-specific Gag-Texo vaccine stimulated Gag-specific effector CD8＋ cytotoxic T lymphocyte （CTL） responses, leading to completely protective, but very limited, therapeutic immunity. In this study, we constructed a recombinant adenoviral vector, adenovirus （AdV）4-1BBL, which expressed mouse 4-1BB ligand （4-1BBL）, and generated transgenic 4-1BBL-engineered OVA-Texo/4.1BSL and Gag-Texo/4.1BSL vaccines by transfecting ovalbumin （OVA）-Texo and Gag-＇rexo cells with AdV4.1BBL, respectively. We demonstrate that the OVA-specific OVA-Texo/4.ZSSL vaccine stimulates more efficient OVA-specific CTL responses （3.26%） compared to OVA-Texo-activated responses （1.98%） in wild-type C57BIJ6 mice and the control OVA-TeXO/Nu, vaccine without transgenic 4-1BBL expression, leading to enhanced therapeutic immunity against 6-day established OVA-expressing B16 melanoma BL6-1OovA cells. OVA-Texo/4.1BBL-stimulated CTLs, which have a CD44＋CD62Lhigh IL-7R＋ phenotype, are likely memory CTL precursors, demonstrating prolonged survival and enhanced differentiation into memory CTLs with functional recall responses and long-term immunity against BL6-1OovA melanoma. In addition, we demonstrate that OVA-Texo/4_ZBBL-Stimulated CTLs up- and downregulate the expression of anti-apoptosis （Bcl2110, Naipl, No13, Pak7 and Tnfrsfllb） and pro-apoptosis （Casp12, Trp63 and Trp73） genes, respectively, by RT2 Profiler PCR array analysis. Importantly, the Gag-specific Gag-Texo/4.1BBL vaccine also stimulates more efficient Gag-specific therapeutic and long-term immunity against HLA-A2/Gag-expressing B 16 melanoma BL6-1OGag/A2 cells than the control Gag-TeXO/NuH vaccine in transgenic HLA-A2 mice. Taken together, our novel Gag-Texo/4-ZBBL vaccine, which is capable of stimulating potent Gag-specific therapeutic and long-term immunity, may represent a new immunotherapeutic vaccine for controlling HIV-1 infection.展开更多
For scientists pursuing drug development for prostate cancer,it is critical that an appropriate ex vivo or in vitro model system is available for study.Cancer research has generally consisted of:(1)finding the means t...For scientists pursuing drug development for prostate cancer,it is critical that an appropriate ex vivo or in vitro model system is available for study.Cancer research has generally consisted of:(1)finding the means to arrest fast growing cancer cells;or(2)(as a compromise)to slow down the excessive rate of cell growth;or in the best case(3)to kill the cancer cells whilst sparing the surrounding normal tissues.As the knowledge of the biological nature of the cancer cell improves,it has become increasingly apparent that such a simplistic attitude to cancer therapy development or indeed diagnosis is rapidly outdated,and a closer liaison between the clinic and the laboratory studies is more important than ever as the author seeks to target specific gene expression pathways,specific signaling pathways,cancer specific mutations and indeed the interactions between cancer cells and their micro-environment,all of which provide a tremendous potential for novel therapeutic development.展开更多
The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initia...The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initiating and propagating properties,while evidence is also emerging about the involvement of specific isoforms in migration,invasiveness and metastasis.Identification of specific ALDH isoforms,which contribute to both drug resistance and aggressiveness of the disease remains a challenge within the complex heterogeneity of prostate cancer.The purpose of this perspective is to dissect functional roles for ALDH in the tumour microenvironment and to evaluate the potential of the ALDH gene family as biomarkers and/or targets for therapeutic intervention.展开更多
Aim:To develop new therapies for prostate cancer,disease heterogeneity must be addressed.This includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic modification.This requ...Aim:To develop new therapies for prostate cancer,disease heterogeneity must be addressed.This includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic modification.This requires more representative models to be used in more innovative ways.Methods:This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient tissue.Several assays were used;alamar blue,colony forming assays,γH2AX and Ki67 immunofluorescence and comet assays.Ptychographic quantitative phase imaging(QPI),a label-free imaging technique,combined with Cell Analysis Toolbox software,was implemented to carry out real-time analysis of cells and to retrieve morphological,kinetic and population data.Results:A combination of radiation and Vorinostat may be more effective than radiation alone.Primary prostate cancer stem-like cells are more resistant to etoposide than more differentiated cells.Analysis of QPI images showed that cell lines and primary cells differ in their size,motility and proliferation rate.A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary culture.Conclusion:Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular heterogeneity.Analysis of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.展开更多
文摘Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.
文摘Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K(HML6) and HERV-K(HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K(HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.
文摘Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.
文摘Many hematopoietic malignancies have oncogenic gene fusions, like BCR-ABL, in their tumor-initiating cells. This implicates the product of the fusion as a powerful cancer-initiating event. In human prostate cancers, despite the detection of numerous similar fusions,
基金supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0501600)Guangzhou Science and Technology Project(2025A04J3327)+1 种基金Cancer Innovative Research Program of Sun Yat-sen University Cancer Center(CIRPSYSUCC-0004)Young Talents Program of Sun Yat-sen University Cancer Center(YTP-SYSUCC-0048).
文摘Background:The epidemiological profiles of gastrointestinal(GI)cancers vary across countries and over time,largely reflecting variations in risk factors and screening practices.We aimed to provide an overview of the current global burden of the five major types of GI cancers and conduct an updated evaluation of the long-term trends of GI cancers.Methods:The updated numbers of new cases and deaths,and age-standardized rates(ASR),of the five GI cancers for 185 countries were sourced from the GLOBOCAN 2022,and presented by cancer site,continent,and human development index(HDI).For 43 countries,annual incidence and mortality data were obtained from the Cancer Incidence in Five Continents Plus and World Health Organization mortality databases,supplemented by the mortality data from the Disease Surveillance Points system for China.We compared the longterm trends of ASRs across countries since 1980,and estimated average annual percent changes(AAPCs)for the recent period 2003-2017.Results:In 2022,there were 4,783,391 new cases and 3,235,719 deaths from the five GI cancers,accounting for 23.9%and 33.2%of all new cancer cases and deaths worldwide,respectively.Cancers of oesophagus,stomach,and liver were more common in Asian and high HDI countries,and colorectal and pancreatic cancer in western and very high HDI countries.Downward trends were observed in almost all countries for gastric cancer and most countries for oesophageal cancer.For colorectal cancer,the most favorable and unfavorable trends were found in 10 and 19 countries respectively.The largest decreases in liver cancer burden were mainly in eastern and southeastern Asia,while increases were seen in North America,Oceania,and Northern Europe,with AAPCs of 3%∼7%for incidence and 2%∼9%for mortality during 2003-2017.Half of the included countries showed increases in pancreatic cancer burden,with the largest AAPCs in Cyprus,Thailand,India,Türkiye,France,and Belarus for incidence,and Türkiye,Thailand,and China for mortality.Conclusions:Deviating patterns were found for GI cancers worldwide.Multisetting studies might provide insights into the underlying etiologies of these cancers,and identify areas where urgent cancer control strategies are needed.
文摘The 2024 updates of the Chinese Society of Clinical Oncology(CSCO)Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China,highlighting the latest advancements in evidence-based medicine,healthcare resource access,and precision medicine in oncology.These updates address disparities in epidemiological trends,clinicopathological characteristics,tumor biology,treatment approaches,and drug selection for colorectal cancer patients across diverse regions and backgrounds.Key revisions include adjustments to evidence levels for intensive treatment strategies,updates to regimens for deficient mismatch repair(dMMR)/microsatellite instability-high(MSI-H)patients,proficient mismatch repair(pMMR)/microsatellite stability(MSS)patients who have failed standard therapies,and rectal cancer patients with low recurrence risk.Additionally,recommendations for digital rectal examination and DNA polymerase epsilon(POLE)/DNA polymerase delta 1(POLD1)gene mutation testing have been strengthened.The 2024CSCOGuidelines are based on both Chinese and international clinical research,aswell as expert consensus,ensuring their relevance and applicability in clinical practice,while maintaining a commitment to scientific rigor,impartiality,and timely updates.
基金Supported by Grants from Ragnar Soderbergs FoundationThe Swedish Children’s Cancer Foundation+9 种基金BILTEMA FoundationFamily Ehring Perssons FoundationSten A Olssons FoundationStichting af Jochnicks FoundationThe Swedish Cancer Society,The Swedish Research Council,the Marta and Gunnar V Philipson FoundationThe Hans and Marit Rausing Charitable FundThe Damman FoundationSwedish Society for Medical Research(SLS),Goljes Memory FoundationMagnus Bergvalls FoundationSwedish Society for Medical Research(SSMF)and Tore Nilsons Foundation
文摘During the last years increasing evidence implies that human cytomegalovirus(CMV) can be attributed to human malignancies arising from numerous tissues. In this perspective, we will review and discuss the potential mechanisms through which CMV infection may contribute to brain tumors by affecting tumor cell initiation, progression and metastasis formation. Recent evidence also suggests that anti-CMV treatment results in impaired tumor growth of CMV positive xenografts in animal models and potentially increased survival in CMV positive glioblastoma patients. Based on these observations and the high tumor promoting capacity of this virus, the classical and novel antiviral therapies against CMV should be revisited as they may represent a great promise for halting tumor progression and lower cancer deaths.
基金Supported by the Institute of Research and Development,Walailak University,Thailand(Grant No.WU55304)
文摘Objective: To determine the cytotoxicity, reduction in nitric oxide production and antioxidative activity of the aqueous leaf extract from Tithonia diversifolia(T. diversifolia) in an in vitro model.Methods: Leaves of T. diversifolia were collected from natural habitats and extracted with distilled water using the decoction method. The cytotoxic effect of the extract in terms of cell viability was determined using RAW264.7 cells and human peripheral blood mononuclear cells(PBMCs) via the mitochondrial respiration method using the MTT reagent. The effect of the extract on lipopolysaccharide(LPS)-induced nitric oxide production in RAW264.7 cells was measured using the Griess reagent. The chemical antioxidant was evaluated by ABTS- and DPPH-radical scavenging assays.Results: The half-maximal cytotoxic concentration values were 145.87 mg/m L and73.67 mg/m L for human PBMCs and RAW264.7 cells, respectively. In the presence of phytohemagglutinin-M, the IC_(50) on PBMCs proliferation was 4.42 mg/m L. The noncytotoxic range of the extracts inhibited LPS-induced nitrite production in RAW264.7 cells with an IC_(50) value of 11.63 mg/m L. To determine the anti-oxidative properties, the N-acetyl cysteine equivalent antioxidant capacity of the extract was(32.62 ± 1.87) and(20.99 ± 2.79)mg N-acetyl cysteine/g extract, respectively determined by the ABTS-radical and DPPHradical assay. However, the extract did not confer death protection in a hydrogen peroxideinduced RAW264.7 co-culturing model.Conclusions: Our study demonstrated the immunomodulation caused by the aqueous leaf extract of T. diversifolia, resulting from the inhibition of phytohemagglutinin-Minduced PBMCs proliferation and LPS-induced nitric oxide production in RAW264.7macrophages. Although the anti-oxidative activity was presented in the chemical-based anti-oxidant assay, the extract cannot protect cell death from stress conditions.
文摘Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.
文摘Sunlight is a known skin carcinogen. Skin cancer is the most common form of cancer in humans, and typically affects sun-exposed parts of the body. Sunny Australia and New Zealand have the highest incidence of skin cancer globally. Clothing provides a protective barrier that reduces the amount of ultraviolet radiation (UVR) reaching the skin. Australia pioneered the development of a relative ranking of the sun-protective capabilities of clothing based on the transmission of UVR through fabric. Standardized Ultraviolet Protection Factor (UPF) measurement procedures and associated labeling specifications are documented in the Australian and New Zealand Standard, AS/NZS 4399:1996. The standard was intended to enable consumers to make informed choices. Since its introduction, this standard has been adopted almost universally by the textile industry, and is still in use almost two decades on, with plans to revise it only commencing recently. However, AS/NZS 4399:1996 does not consider garment design, particularly in relation to body surface coverage. Although swim-shirts have grown in popularity in Australia since the late 1990s, particularly among children, clothing remains under-utilized as a form of sun-protection in contemporary society. Skin cancer prevention campaigns should emphasize the sun-protective benefits of clothing and collaboration with the fashion industry is urgently needed to improve the aesthetic appeal, comfort, durability and affordability of sun-protective clothing to increase its popularity in skin cancer prone populations. In light of recent evidence showing that high UPF clothing which covers more of the body surface reduces pigmented mole development in children (major risk factor for melanoma), the rating system for sun-protective clothing should incorporate body surface covered as well as the UPF of the fabric. We discuss progress towards developing a protocol for measuring the extent of coverage of sun-protective garments. Once fully evaluated and refined, the testing protocol developed from this research may influence future revisions of international standards for evaluating and classifying sun-protective clothing.
文摘Sympathetic neuronal differentiation is associated with favorable prognosis of neuroblastoma （NB）, the most common extra-cranial solid tumor of early childhood. Differentiation agents have proved useful in clinical protocols of NB treatment, but using them as a sole treatment is not sufficient to induce tumor elimination in patients. Therefore, complementary approaches, such as immunotherapy, are warranted. Here we demonstrate that differentiation of NB cell lines and ex vivo isolated tumor cells in response to physiological or pharmacological stimuli is associated with acquisition of increased antigenicity. This manifests as increased expression of surface major histocompatibility class I complexes and ICAM-1 molecules and translates into increased sensitivity of NB cells to lysis by cytotoxic T lymphocytes （CTLs） and natural killer （NK） cells. The latter is paralleled by enhanced ability of differentiated cells to form immune conjugates and bind increased amounts of granzyme B to the cell surface. We demonstrate, for the first time, that, regardless of the stimulus applied, the differentiation state in NBs is associated with increased tumor antigenicity that enables more efficient elimination of tumor cells by cytotoxic lymphocytes and paves the way for combined application of differentiation-inducing agents and immunotherapy as an auxiliary approach in NB patients.
基金supported by the Dutch Cancer Society(KUN 2019-12640).
文摘Currently,lymph node metastases(LNM)are seen as the gateway to distant metastases in CRC and play a crucial role in the Tumor Node Metastasis(TNM)staging system[1,2].Tumor deposits(TD)have been identified as another histological feature with a strong prognostic impact but are currently only deemed clinically relevant in the absence of LNM[2,3].TD are clusters of tumor cells in the fat surrounding the bowel and are often associated with nerves,vessels and lymphatic tissue,giving the cancer cells access to multiple routes of spread[4].
文摘Genetic alterations to serine-threonine kinase 11(STK11)have been implicated in Peutz-Jeghers syndrome and tumorigenesis.Further exploration of the context-specific roles of liver kinase B1(LKB1;encoded by STK11)observed that it regulates AMP-activated protein ki-nase(AMPK)and AMPK-related kinases.Given that both migration and proliferation are enhanced with the loss of LKB1 activity combined with the prevalence of STK11 genetic alter-ations in cancer biopsies,LKB1 was markedas a tumor suppressor.However,the roleof LKB1 in tumorigenesis is paradoxical as LKB1 activates autophagy and reactive oxygen species scav-enging while dampening anoikis,which contribute to cancer cell survival.Due to the pro-tumor-igenic properties of LKB1,targeting LKB1 pathways is now relevant for cancer treatment.With the recent successes of targeting LKB1 signaling in research and clinical settings,and enhanced cytotoxicity of chemical compounds in LKB1-deficient tumors,there is now a need for LKB1 in-hibitors.However,validating LKB1 inhibitors is challenging as LKB1 adaptor proteins,nucleocy-toplasmic shuttling,and splice variants all manipulate LKB1 activity.Furthermore,STE-20-related kinase adaptor protein(STRAD)and mouse protein 25 dictate LKB1 cellular localization and kinase activity.For these reasons,prior to assessing the efficacy and potency of pharmaco-logical candidates,the functional status of LKB1 needs to be defined.Therefore,to improve the understanding of LKB1 in physiology and oncology,this review highlights the role of LKB1 in tumorigenesis and addresses the therapeutic relevancy of LKB1 inhibitors..
文摘Pancreatic ductal adenocarcinoma(PDAC)remains one of medicine’s most urgent areas of unmet need.With 5-year survival rates of∼11%,PDAC is set to become the second leading cause of cancer related deaths by 2040[1].The complex tumour microenvironment(TME)in PDAC,responsible for poor prognosis,is comprised of extracellular matrix(ECM)proteins and multiple cell types;with pancreatic stellate cells(PSCs),which become activated cancer associated fibroblasts(CAFs),being regarded as key orchestrators of the TME.We have demonstrated that treatment with all-trans retinoic acid(ATRA)can render activated PSCs(aPSC)to a quiescent(qPSC)phenotype(shift to G1 phase of cell cycle and other features[2]),resulting in stromal remodelling and thus,influencing cancer cell co-targeting with chemotherapy in patients[3].This has resulted in the use of ATRA along with standard-of-care chemotherapy in the Stromal TARgeting for PAncreatic Cancer(STARPAC)clinical trial,with promising results[4].These clinically relevant[5],exciting potential therapeutic benefits of stromal co-targeting through rendering PSCs quiescent[6],along with predictive inflammation-related biomarkers[7],and increased focus on cellular therapeutics such as NK cells,led us to postulate potential targetable PSC-immune cell interactions which may uncover a comprehensive therapeutic strategy for treating hitherto,incurable PDAC.
文摘Human immunodeficiency virus type-1 （HIV-1）-specific dendritic cell （DC） vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. We previously demonstrated that the HIV-1 Gag-specific Gag-Texo vaccine stimulated Gag-specific effector CD8＋ cytotoxic T lymphocyte （CTL） responses, leading to completely protective, but very limited, therapeutic immunity. In this study, we constructed a recombinant adenoviral vector, adenovirus （AdV）4-1BBL, which expressed mouse 4-1BB ligand （4-1BBL）, and generated transgenic 4-1BBL-engineered OVA-Texo/4.1BSL and Gag-Texo/4.1BSL vaccines by transfecting ovalbumin （OVA）-Texo and Gag-＇rexo cells with AdV4.1BBL, respectively. We demonstrate that the OVA-specific OVA-Texo/4.ZSSL vaccine stimulates more efficient OVA-specific CTL responses （3.26%） compared to OVA-Texo-activated responses （1.98%） in wild-type C57BIJ6 mice and the control OVA-TeXO/Nu, vaccine without transgenic 4-1BBL expression, leading to enhanced therapeutic immunity against 6-day established OVA-expressing B16 melanoma BL6-1OovA cells. OVA-Texo/4.1BBL-stimulated CTLs, which have a CD44＋CD62Lhigh IL-7R＋ phenotype, are likely memory CTL precursors, demonstrating prolonged survival and enhanced differentiation into memory CTLs with functional recall responses and long-term immunity against BL6-1OovA melanoma. In addition, we demonstrate that OVA-Texo/4_ZBBL-Stimulated CTLs up- and downregulate the expression of anti-apoptosis （Bcl2110, Naipl, No13, Pak7 and Tnfrsfllb） and pro-apoptosis （Casp12, Trp63 and Trp73） genes, respectively, by RT2 Profiler PCR array analysis. Importantly, the Gag-specific Gag-Texo/4.1BBL vaccine also stimulates more efficient Gag-specific therapeutic and long-term immunity against HLA-A2/Gag-expressing B 16 melanoma BL6-1OGag/A2 cells than the control Gag-TeXO/NuH vaccine in transgenic HLA-A2 mice. Taken together, our novel Gag-Texo/4-ZBBL vaccine, which is capable of stimulating potent Gag-specific therapeutic and long-term immunity, may represent a new immunotherapeutic vaccine for controlling HIV-1 infection.
基金support of my research in this area by grants from Prostate Cancer UK and Charity Soul。
文摘For scientists pursuing drug development for prostate cancer,it is critical that an appropriate ex vivo or in vitro model system is available for study.Cancer research has generally consisted of:(1)finding the means to arrest fast growing cancer cells;or(2)(as a compromise)to slow down the excessive rate of cell growth;or in the best case(3)to kill the cancer cells whilst sparing the surrounding normal tissues.As the knowledge of the biological nature of the cancer cell improves,it has become increasingly apparent that such a simplistic attitude to cancer therapy development or indeed diagnosis is rapidly outdated,and a closer liaison between the clinic and the laboratory studies is more important than ever as the author seeks to target specific gene expression pathways,specific signaling pathways,cancer specific mutations and indeed the interactions between cancer cells and their micro-environment,all of which provide a tremendous potential for novel therapeutic development.
基金We wish to acknowledge Prostate Cancer UK(RIA15-ST2-022&PhD grant S12-027)for finan cial support and sponsorship,and Yaqeen Sawalha for producing figures for this manuscript.
文摘The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some controversy.Many studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initiating and propagating properties,while evidence is also emerging about the involvement of specific isoforms in migration,invasiveness and metastasis.Identification of specific ALDH isoforms,which contribute to both drug resistance and aggressiveness of the disease remains a challenge within the complex heterogeneity of prostate cancer.The purpose of this perspective is to dissect functional roles for ALDH in the tumour microenvironment and to evaluate the potential of the ALDH gene family as biomarkers and/or targets for therapeutic intervention.
基金funded by a PCUK Innovation Award-RIA15-ST2-022.SK was supported by a White Rose Fund studentship.
文摘Aim:To develop new therapies for prostate cancer,disease heterogeneity must be addressed.This includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic modification.This requires more representative models to be used in more innovative ways.Methods:This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient tissue.Several assays were used;alamar blue,colony forming assays,γH2AX and Ki67 immunofluorescence and comet assays.Ptychographic quantitative phase imaging(QPI),a label-free imaging technique,combined with Cell Analysis Toolbox software,was implemented to carry out real-time analysis of cells and to retrieve morphological,kinetic and population data.Results:A combination of radiation and Vorinostat may be more effective than radiation alone.Primary prostate cancer stem-like cells are more resistant to etoposide than more differentiated cells.Analysis of QPI images showed that cell lines and primary cells differ in their size,motility and proliferation rate.A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary culture.Conclusion:Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular heterogeneity.Analysis of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.
