Descriptive Study on Liver Cancer among Alcohol consumer and Smokers

Liver cancer is one of the significant cancer types affecting the human population taking their lives. The study aimed to analyze the situation of liver cancer among alcohol consumers and smokers together, and it was conducted in BPKMCH, Chitwan. The data was collected from the year 2009 to 2013 AD. Randomly selected 160 cancer cases and analyzed the data. The finding suggested that most of the liver cancer patients drank alcohol and smoking cigarettes. The study indicated that there is still a need to investigate further the role of alcohol and smoking in the cancer genesis among them.

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A pan-cancer study on characteristic of CDK4/6 amplification between Chinese and Western patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15074 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15074-e15074

Author(s):

Yamin Zhang ◽

Zilin Cui ◽

Rui Shi ◽

Xiaolong Liu ◽

Yang Li ◽

...

Keyword(s):

Soft Tissue ◽

Liver Cancer ◽

Soft Tissue Sarcoma ◽

Lung Adenocarcinoma ◽

Ovarian Carcinoma ◽

Cancer Patients ◽

Stomach Carcinoma ◽

Chinese Cohort ◽

Cancer Types ◽

Pan Cancer

e15074 Background: CDK4/6 kinases associate with cyclin D proteins during transition from G1 to S phase of the cell cycle. Amplification of CDK4/6 may elicit the activity of cyclin D, which hyperphosphorylates RB, ultimately leading to uncontrolled cell proliferation. Currently, three CDK4/6 inhibitors are used in breast cancer, ovarian cancer and sarcoma. Herein, we investigate the prevalence of CDK4/6 amplification in Chinese and Western cancer patients, hope to find more cancer subtypes with CDK4/6 amplification. Methods: Next-generation sequencing data and clinical data were collected from 10828 TCGA pan-cancer patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 4181 Chinese pan-cancer patients (Chinese cohort). CDK4 and CDK6 amplification were calculated on the two cohorts following the same criteria. Results: In total, 182 (4.4%) of the 4181 Chinese patients and 529 (4.9%) of the 10828 Western patients had CDK4 amplification, 133 (3.2%) of the 4181 Chinese patients and 475 (4.4%) of the 10828 Western patients had CDK6 amplification. In Western cohort, the top 5 CDK4 amplification-associated cancer types were sarcoma, glioblastoma multiforme, lung adenocarcinoma, ovarian carcinoma, and adrenocortical carcinoma, and the top 5 CDK6 amplification-associated cancer types were esophageal carcinoma, ovarian carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, sarcoma. In Chinese cohort, the top 5 CDK4 amplification-associated cancer types were lung adenocarcinoma, melanoma, sarcoma, stomach carcinoma, liver cancer, and the top 5 CDK6 amplification-associated cancer types were lung adenocarcinoma, stomach carcinoma, liver cancer, melanoma, glioma. In addition, CDK4 amplification in Chinese cohort, 22 (11%) of the 203 Chinese bone and soft tissue sarcoma patients had CDK4 amplification, and 4 (2%) of the 203 had CDK6 amplification. Bone and soft tissue sarcoma types with CDK4 / 6 amplification including soft tissue sarcoma, bone cancer, fibrosarcoma, chondrosarcoma, rhabdomyosarcoma, liposarcoma, synovial sarcoma. Conclusions: Our study provided a characteristic of CDK4/6 amplification in Chinese and Western pan-cancer patients. Analysis revealed frequent CDK4 / 6 amplification in lung cancer, sarcoma, stomach carcinoma, ovarian carcinoma and liver cancer. It is suggested patient with these cancer types may potentially benefit from CDK4/6 inhibitor.

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Landscape Profiling Analysis of DPP4 in Malignancies: Therapeutic Implication for Tumor Patients With Coronavirus Disease 2019

Frontiers in Oncology ◽

10.3389/fonc.2021.624899 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lingling Shu ◽

Yang Liu ◽

Jinyuan Li ◽

Xiaoping Wu ◽

Yang Li ◽

...

Keyword(s):

Cancer Patients ◽

Critical Role ◽

Therapeutic Effects ◽

Strong Correlations ◽

Tumor Patients ◽

Dipeptidyl Peptidase 4 ◽

Specific Tumor ◽

Cancer Types ◽

Profiling Analysis

Severe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by pneumonia, lymphopenia, and cytokine storms. Patients with underlying conditions, and especially cancer patients with impaired immunity, are particularly vulnerable to SARS-CoV-2 infection and complications. Although angiotensin converting enzyme II (ACE2) has been identified as a cellular binding receptor for SARS-CoV-2, immunopathological changes in severe cancer patients support the investigation of additional potential receptors such as dipeptidyl peptidase 4 (DPP4), a key immunoregulator. However, a comprehensive profiling analysis of DPP4 in malignancies remains obscure. In this study, using different datasets, we demonstrated the expression of DPP4 in healthy tissues and pan-cancers, showing the risk of different cancer types towards SARS-CoV-2 infection according to DPP4 expression levels. DPP4 expression was positively correlated with infiltrating levels of various immune cells and showed strong correlations with diverse immune marker sets in pan-cancer patients analyzed by Tumor Immune Estimation Resource (TIMER). These findings suggest that increased DPP4 expression in specific cancer patients might account for the high susceptibility to SARS-CoV-2 infection and the induction of cytokine storms. Due to the critical role of DPP4 in immunometabolism, our results indicate that pharmacological inhibition of DPP4 might provide beneficial therapeutic effects for SARS-CoV-2 treatment together with other strategies in specific tumor patients.

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Measurement of Thrombin Generation Is a Positive Predictive Biomarker of V enous Thromboembolism (VTE) in Metastatic Cancer Patients Enrolled in the Hypercan Study

Blood ◽

10.1182/blood.v126.23.654.654 ◽

2015 ◽

Vol 126 (23) ◽

pp. 654-654 ◽

Cited By ~ 2

Author(s):

Anna Falanga ◽

Marina Marchetti ◽

Cristina Verzeroli ◽

Cinzia Giaccherini ◽

Giovanna Masci ◽

...

Keyword(s):

Cancer Patients ◽

Healthy Subjects ◽

Metastatic Cancer ◽

Breast Cancer Patients ◽

Vein Thrombosis ◽

Kaplan Meier ◽

Cancer Types ◽

D Dimer

Abstract Introduction The HYPERCAN study is an ongoing prospective Italian multicenter trial (Thromb.Res. 2014, Suppl 2, 182), designed to evaluate the role of laboratory hypercoagulation screening to predict early diagnosis (in healthy subjects), or prognosis and response to therapy in patients with either limited or metastatic cancers. Four cancer types are included, i.e. non-small cell lung [NSCL], gastric, colorectal, and breast cancers. The occurrence of clinically manifest VTE events, confirmed by objective diagnostic tests, is also recorded. Patients are followed up for 5 years or death. Aim In a group of patients with metastatic cancer enrolled in the HYPERCAN program, we wanted to evaluate the role of thrombin generation assay (TG), fibrinogen, and D-dimer levels in predicting the occurrence of VTE in the follow up. Methods As of June 2015, overall 831 patients with metastatic cancer have been enrolled. According to protocol, blood samples from these patients are collected at enrollment (baseline), after 3 and 6 chemotherapy cycles, and at end of treatment, or earlier if cancer disease progression. We measured the levels of TG, fibrinogen, and D-dimer in the baseline citrated plasma samples from the first 281 patients enrolled into the study (158 M/123 F; median age 64 years, range 32-84; NSCL = 56.2%, gastric = 11.1%, colorectal = 14.6%, breast = 18.1%). TG was measured by the Calibrated automated thrombogram (CAT assay, STAGO, France) at 5pM TF and results expressed as endogenous thrombin potential (ETP), fibrinogen and D-dimer were measured by commercial assays (Q.F.A. Thrombin; D-dimer HS; Werfen, Italy). Cut-off values were established by ROC curves; Kaplan Meier analysis was performed to define the VTE risk. Results Overall the patient baseline ETP values as well as the fibrinogen and D-Dimer levels were significantly greater than those of a control group of healthy subjects (p<0.0001). Among the cancer types, ETP values were highest in patients with NSCL cancer, and lowest in those with gastric cancer (1899±517 nM*min vs 1622±550 nM*min; p=0.024). D-dimer and fibrinogen levels were greatest in gastric (801±186 ng/ml) and NSCL (484±190 mg/dl) cancers, respectively, and were both lowest in breast cancer patients. After a median follow up of 473 days, overall 37 VTE events were recorded in 36 patients: 16 pulmonary embolism (PE), 16 deep vein thrombosis (DVT), 3 superficial vein thrombosis, and 1 PE + DVT. Of these events, 69% occurred in NSCL, 17% in colon, 8.5% in gastric, and 5.5% in breast cancer patients. Median time to VTE was 5 months from enrollment, >80% of VTE developed during chemotherapy. Baseline ETP levels were significantly higher in patients with VTE than in patients without VTE (2020±618 nM*min vs 1799±467 nM*min; p=0.017). Univariate analysis (Kaplan-Meier) showed that patients with ETP>1750 nM*min had about 3-fold higher risk of developing VTE than those with ETP<1750 nM*min (HR:2.841, 95% CI 1.42-5.69 p=0.002). ETP predictive value remained significant by multivariate analysis after correction for age, gender, and tumor site (HR: 2.341, 95% CI 1.15-4.75, p=0.019). Differently, the baseline levels of D-dimer and fibrinogen did not significantly predict for VTE. Conclusions These results reveal that ETP is a valuable marker in predicting VTE in metastatic cancer patients, therefore it can help to optimize the identification of the high risk subjects, which remains an important challenge and may improve the design of interventional studies of efficacy and safety of primary thromboprophylaxis in cancer patients during chemotherapy. Project funded by AIRC "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)". Disclosures Santoro: Celgene: Research Funding.

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Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives

Cancers ◽

10.3390/cancers13123035 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3035

Author(s):

Alessandra Dall'Acqua ◽

Michele Bartoletti ◽

Nastaran Masoudi-Khoram ◽

Roberto Sorio ◽

Fabio Puglisi ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Therapeutic Targets ◽

Metastatic Breast ◽

Molecular Alterations ◽

Estrogen Receptor Positive ◽

Cancer Types ◽

Almost All ◽

Tumor Types

Alterations in components of the cell-cycle machinery are present in essentially all tumor types. In particular, molecular alterations resulting in dysregulation of the G1 to S phase transition have been observed in almost all human tumors, including ovarian cancer. These alterations have been identified as potential therapeutic targets in several cancer types, thereby stimulating the development of small molecule inhibitors of the cyclin dependent kinases. Among these, CDK4 and CDK6 inhibitors confirmed in clinical trials that CDKs might indeed represent valid therapeutic targets in, at least some, types of cancer. CDK4 and CDK6 inhibitors are now used in clinic for the treatment of patients with estrogen receptor positive metastatic breast cancer and their clinical use is being tested in many other cancer types, alone or in combination with other agents. Here, we review the role of CDK4 and CDK6 complexes in ovarian cancer and propose the possible use of their inhibitors in the treatment of ovarian cancer patients with different types and stages of disease.

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Olfm4 Is Highly Expressed In Liver Cancer Patients And As A Biomarker And Therapeutic Target For Liver Cancer

10.21203/rs.3.rs-686335/v1 ◽

2021 ◽

Author(s):

Qingzhu Song

Keyword(s):

Liver Cancer ◽

Cancer Patients ◽

Cancer Tissue ◽

Cancer Cell Proliferation ◽

Mrna Expression Level ◽

Healthy Individuals ◽

Predictive Capacity ◽

Novel Drugs ◽

Liver Cancers ◽

Cancer Types

Abstract Liver cancer is one of important cancer types causing a large number death in the world, and the incidence is still increasing. Conventional therapies against liver cancer are not satisfied and pathogenesis of liver cancer remains unclear. Thus, the more effective therapies are needed to treat liver cancers, and the discovery of key genes involving in pathogenesis of liver cancers is important for developing more effective therapies to treat liver cancer. In the present study, we found that OLFM4 blood level is higher in liver cancer patients than in healthy individuals, and mRNA expression level in liver cancer tissue than in liver paracancerous tissues. OLFM4 has high predictive capacity as a biomarker for liver cancer and closely correlated to tumor size. Importantly, it is confirmed that OLFM4 contributes to cancer cell proliferation, and HIF-1α involves in this activity. We believe that OLFM4/HIF-1α axis might be a target signaling pathway for developing novel drugs to treat liver cancer.

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Integration of adeno-associated virus (AAV) into the genomes of most Thai and Mongolian liver cancer patients does not induce oncogenesis

BMC Genomics ◽

10.1186/s12864-021-08098-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Alejandro A. Schäffer ◽

Dana A. Dominguez ◽

Lesley M. Chapman ◽

E. Michael Gertz ◽

Anuradha Budhu ◽

...

Keyword(s):

Liver Cancer ◽

Cancer Patients ◽

The Cancer Genome Atlas ◽

Adeno Associated Virus ◽

Asian Patients ◽

Positional Bias ◽

Cancer Genome Atlas ◽

Almost All ◽

Whole Transcriptome

Abstract Background Engineered versions of adeno-associated virus (AAV) are commonly used in gene therapy but evidence revealing a potential oncogenic role of natural AAV in hepatocellular carcinoma (HCC) has raised concerns. The frequency of potentially oncogenic integrations has been reported in only a few populations. AAV infection and host genome integration in another type of liver cancer, cholangiocarcinoma (CCA), has been studied only in one cohort. All reported oncogenic AAV integrations in HCC come from strains resembling the fully sequenced AAV2 and partly sequenced AAV13. When AAV integration occurs, only a fragment of the AAV genome is detectable in later DNA or RNA sequencing. The integrated fragment is typically from the 3’ end of the AAV genome, and this positional bias has been only partly explained. Three research groups searched for evidence of AAV integration in HCC RNAseq samples in the Cancer Genome Atlas (TCGA) but reported conflicting results. Results We collected and analyzed whole transcriptome and viral capture DNA sequencing in paired tumor and non-tumor samples from two liver cancer Asian cohorts from Thailand (N = 147, 47 HCC and 100 intrahepatic cholangiocarcinoma (iCCA)) and Mongolia (N = 70, all HCC). We found only one HCC patient with a potentially oncogenic integration of AAV, in contrast to higher frequency reported in European patients. There were no oncogenic AAV integrations in iCCA patients. AAV genomic segments are present preferentially in the non-tumor samples of Thai patients. By analyzing the AAV genome positions of oncogenic and non-oncogenic integrated fragments, we found that almost all the putative oncogenic integrations overlap the X gene, which is present and functional only in the strain AAV2 among all fully sequenced strains. This gene content difference could explain why putative oncogenic integrations from other AAV strains have not been reported. We resolved the discrepancies in previous analyses of AAV presence in TCGA HCC samples and extended it to CCA. There are 12 TCGA samples with an AAV segment and none are in Asian patients. AAV segments are present in preferentially in TCGA non-tumor samples, like what we observed in the Thai patients. Conclusions Our findings suggest a minimal AAV risk of hepatocarcinogenesis in Asian liver cancer patients. The partial genome presence and positional bias of AAV integrations into the human genome has complicated analysis of possible roles of AAV in liver cancer.

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Molecular Mechanisms Underlying Autophagy-Mediated Treatment Resistance in Cancer

Cancers ◽

10.3390/cancers11111775 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1775 ◽

Cited By ~ 18

Author(s):

Cally J. Ho ◽

Sharon M. Gorski

Keyword(s):

Tumor Progression ◽

Signaling Pathways ◽

Cancer Patients ◽

Targeted Therapies ◽

Molecular Mechanisms ◽

Treatment Resistance ◽

Akt Signaling ◽

Diagnostic Tools ◽

Cancer Types

Despite advances in diagnostic tools and therapeutic options, treatment resistance remains a challenge for many cancer patients. Recent studies have found evidence that autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation and recycling, contributes to treatment resistance in different cancer types. A role for autophagy in resistance to chemotherapies and targeted therapies has been described based largely on associations with various signaling pathways, including MAPK and PI3K/AKT signaling. However, our current understanding of the molecular mechanisms underlying the role of autophagy in facilitating treatment resistance remains limited. Here we provide a comprehensive summary of the evidence linking autophagy to major signaling pathways in the context of treatment resistance and tumor progression, and then highlight recently emerged molecular mechanisms underlying autophagy and the p62/KEAP1/NRF2 and FOXO3A/PUMA axes in chemoresistance.

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