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Article ; Online: Recent Trends in Multipotent Human Mesenchymal Stem/Stromal Cells: Learning from History and Advancing Clinical Applications.

Dzobo, Kevin

Omics : a journal of integrative biology

2021 Volume 25, Issue 6, Page(s) 342–357

Abstract: Early cell biology reports demonstrated the presence of cells with stem-like properties in bone marrow, with both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem ... ...

Abstract	Early cell biology reports demonstrated the presence of cells with stem-like properties in bone marrow, with both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multilineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and versatile potentials, MSCs are leveraged in many applications in medicine such as oncology, bioprinting, and as recent as therapeutics discovery and innovation for COVID-19. To date, studies indicate that MSCs have varied differentiation capabilities into different cell types, and demonstrate immunomodulating and anti-inflammatory properties. Different microenvironments or niche for MSCs and their resulting heterogeneity may influence attendant cellular behavior and differentiation capacity. The potential clinical applications of MSCs and exosomes derived from these cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. There is ample reason to think, as discussed in this expert review that the future looks bright and promising for MSC research, with many clinical trials under way to ascertain their clinical utility. This review provides a synthesis of the latest advances and trends in MSC research to allow for broad and critically informed use of MSCs. Early observations of the presence of these cells in the bone marrow and their remarkable differentiation capabilities and immunomodulation are also presented.
MeSH term(s)	Cell Differentiation ; Humans ; Immunomodulation ; Mesenchymal Stem Cells/immunology ; Mesenchymal Stem Cells/physiology ; Regenerative Medicine ; Stem Cell Niche ; Tissue Engineering
Language	English
Publishing date	2021-05-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2021.0049
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Article ; Online: What to Do for Increasing Cancer Burden on the African Continent? Accelerating Public Health Diagnostics Innovation for Prevention and Early Intervention on Cancers.

Dzobo, Kevin

Omics : a journal of integrative biology

2021 Volume 25, Issue 9, Page(s) 567–579

Abstract: No other place illustrates the increasing burden of cancer than in Africa and in particular, sub-Saharan Africa. Many of the individuals to be diagnosed with cancer will be in low-resource settings in the future due to, for example, an increase in ... ...

Abstract	No other place illustrates the increasing burden of cancer than in Africa and in particular, sub-Saharan Africa. Many of the individuals to be diagnosed with cancer will be in low-resource settings in the future due to, for example, an increase in populations and aging, and high co-morbidity with infections with viruses such as human immunodeficiency virus (HIV) and human papillomavirus (HPV), as well as the presence of infectious agents linked to cancer development. Due to lack of prevention and diagnostic innovation, patients present with advanced cancers, leading to poor survival and increased mortality. HIV infection-associated cancers such as B cell lymphomas, Kaposi's sarcoma, and HPV-associated cancers such as cervical cancer are particularly noteworthy in this context. Recent reports show that a host of other cancers are also associated with viral infection and these include lung, oral cavity, esophageal, and pharyngeal, hepatocellular carcinoma, and anal and vulvar cancers. This article examines the ways in which diagnostic innovation empowered by integrative biology and informed by public health priorities can improve cancer prevention or early intervention in Africa and beyond. In addition, I argue that because diagnostic biomarkers can often overlap with novel therapeutic targets, diagnostics research and development can have broader value for and impact on medical innovation.
MeSH term(s)	Africa South of the Sahara ; Female ; HIV Infections/diagnosis ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; Humans ; Papillomaviridae ; Public Health ; Uterine Cervical Neoplasms/diagnosis ; Uterine Cervical Neoplasms/prevention & control
Language	English
Publishing date	2021-08-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2021.0098
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Article ; Online: Integrins Within the Tumor Microenvironment: Biological Functions, Importance for Molecular Targeting, and Cancer Therapeutics Innovation.

Dzobo, Kevin

Omics : a journal of integrative biology

2021 Volume 25, Issue 7, Page(s) 417–430

Abstract: Many cellular functions important for solid tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell attachment receptors. With recent studies emphasizing the role of the tumor microenvironment (TME) in ... ...

Abstract	Many cellular functions important for solid tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell attachment receptors. With recent studies emphasizing the role of the tumor microenvironment (TME) in tumor initiation and progression, it is not surprising that considerable attention is being paid to integrins. Several integrin antagonists are under clinical trials, with many demonstrating promising activity in patients with different cancers. A deeper knowledge of the functions of integrins within the TME is still required and might lead to better inhibitors being discovered. Integrin expression is commonly dysregulated in many tumors with integrins playing key roles in signaling as well as promotion of tumor cell invasion and migration. Integrins also play a major role in adhesion of circulating tumor cells to new sites and the resulting formation of secondary tumors. Furthermore, integrins have demonstrated the ability to promoting stem cell-like properties in tumor cells as well as drug resistance. Anti-integrin therapies rely heavily on the doses or concentrations used as these determine whether the drugs act as antagonists or as integrin agonists. This expert review offers the latest synthesis in terms of the current knowledge of integrins functions within the TME and as potential molecular targets for cancer therapeutics innovation.
MeSH term(s)	Humans ; Integrins/genetics ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/genetics ; Signal Transduction ; Tumor Microenvironment
Chemical Substances	Integrins
Language	English
Publishing date	2021-06-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2021.0069
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Article ; Online: Coronavirus Disease 19 and Future Ecological Crises: Hopes from Epigenomics and Unraveling Genome Regulation in Humans and Infectious Agents.

Dzobo, Kevin

Omics : a journal of integrative biology

2021 Volume 25, Issue 5, Page(s) 269–278

Abstract: With coronavirus disease 19 (COVID-19), we have witnessed a shift from public health to planetary health and a growing recognition of the importance of systems science in developing effective solutions against pandemics in the 21st century. COVID-19 and ... ...

Abstract	With coronavirus disease 19 (COVID-19), we have witnessed a shift from public health to planetary health and a growing recognition of the importance of systems science in developing effective solutions against pandemics in the 21st century. COVID-19 and the history of frequent infectious outbreaks in the last two decades suggest that COVID-19 is likely a dry run for future ecological crises. Now is the right time to plan ahead and deploy the armamentarium of systems science scholarship for planetary health. The science of epigenomics, which investigates both genetic and nongenetic traits regarding heritable phenotypic alterations, and new approaches to understanding genome regulation in humans and pathogens offer veritable prospects to boost the global scientific capacities to innovate therapeutics and diagnostics against novel and existing infectious agents. Several reversible epigenetic alterations, such as chromatin remodeling and histone methylation, control and influence gene expression. COVID-19 lethality is linked, in part, to the cytokine storm, age, and status of the immune system in a given person. Additionally, due to reduced human mobility and daily activities, effects of the pandemic on the environment have been both positive and negative. For example, reduction in environmental pollution and lesser extraction from nature have potential positive corollaries on water and air quality. Negative effects include pollution as plastics and other materials were disposed in unconventional places and spaces in the course of the pandemic. I discuss the opportunities and challenges associated with the science of epigenomics, specifically with an eye to inform and prevent future ecological crises and pandemics that are looming on the horizon in the 21st century. In particular, this article underscores that epigenetics of both viruses and the host may influence virus infectivity and severity of attendant disease.
MeSH term(s)	Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/genetics ; COVID-19/virology ; Ecology ; Environmental Health ; Epigenesis, Genetic ; Epigenomics ; Gene Expression Regulation ; Global Health ; Host Microbial Interactions/genetics ; Humans ; Pandemics ; SARS-CoV-2/pathogenicity
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2021-04-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2021.0024
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Article ; Online: The Role of Viruses in Carcinogenesis and Molecular Targeting: From Infection to Being a Component of the Tumor Microenvironment.

Dzobo, Kevin

Omics : a journal of integrative biology

2021 Volume 25, Issue 6, Page(s) 358–371

Abstract: About a tenth of all cancers are caused by viruses or associated with viral infection. Recent global events including the coronavirus disease-2019 (COVID-19) pandemic means that human encounter with viruses is increased. Cancer development in individuals ...

Abstract	About a tenth of all cancers are caused by viruses or associated with viral infection. Recent global events including the coronavirus disease-2019 (COVID-19) pandemic means that human encounter with viruses is increased. Cancer development in individuals with viral infection can take many years after infection, demonstrating that the involvement of viruses in cancer development is a long and complex process. This complexity emanates from individual genetic heterogeneity and the many steps involved in cancer development owing to viruses. The process of tumorigenesis is driven by the complex interaction between several viral factors and host factors leading to the creation of a tumor microenvironment (TME) that is ideal and promotes tumor formation. Viruses associated with human cancers ensure their survival and proliferation through activation of several cellular processes including inflammation, migration, and invasion, resistance to apoptosis and growth suppressors. In addition, most human oncoviruses evade immune detection and can activate signaling cascades including the PI3K-Akt-mTOR, Notch and Wnt pathways associated with enhanced proliferation and angiogenesis. This expert review examines and synthesizes the multiple biological factors related to oncoviruses, and the signaling cascades activated by these viruses contributing to viral oncogenesis. In particular, I examine and review the Epstein-Barr virus, human papillomaviruses, and Kaposi's sarcoma herpes virus in a context of cancer pathogenesis. I conclude with a future outlook on therapeutic targeting of the viruses and their associated oncogenic pathways within the TME. These anticancer strategies can be in the form of, but not limited to, antibodies and inhibitors.
MeSH term(s)	Alphapapillomavirus/physiology ; Carcinogenesis ; Cell Transformation, Viral ; Epstein-Barr Virus Infections/pathology ; Epstein-Barr Virus Infections/virology ; Herpesvirus 4, Human/physiology ; Herpesvirus 8, Human/physiology ; Humans ; Molecular Targeted Therapy ; Neoplasms/pathology ; Neoplasms/therapy ; Neoplasms/virology ; Papillomavirus Infections/pathology ; Papillomavirus Infections/virology ; Retroviridae/physiology ; Retroviridae Infections/pathology ; Retroviridae Infections/virology ; Sarcoma, Kaposi/pathology ; Sarcoma, Kaposi/virology ; Signal Transduction ; Tumor Microenvironment ; Tumor Virus Infections/pathology ; Tumor Virus Infections/virology
Language	English
Publishing date	2021-05-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2021.0052
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Article ; Online: Taking a Full Snapshot of Cancer Biology: Deciphering the Tumor Microenvironment for Effective Cancer Therapy in the Oncology Clinic.

Dzobo, Kevin

Omics : a journal of integrative biology

2020 Volume 24, Issue 4, Page(s) 175–179

Abstract: A bottleneck that is hindering therapeutics innovation in cancers is the current lack of integration of what we have learned in tumor biology as well as the tumor microenvironment (TME). This is because tumors are complex tissues composed of cancer cells, ...

Abstract	A bottleneck that is hindering therapeutics innovation in cancers is the current lack of integration of what we have learned in tumor biology as well as the tumor microenvironment (TME). This is because tumors are complex tissues composed of cancer cells, stromal cells, and the extracellular matrix (ECM). Although genetic alterations might cause the initial uncontrolled growth, resistance to apoptosis in cancer cells and stromal cells play additional key roles within the TME and thus influence tumor initiation, progression, therapy resistance, and metastasis. Therapies targeting cancer cells are usually insufficient when the stromal component of the TME causes therapy resistance. For innovation in cancer treatment and to take a full snapshot of cancer biology, anticancer drug design must, therefore, target both cancer cells and the stromal component. This expert review critically examines the TME components such as cancer-associated fibroblasts and ECM that can be reprogrammed to create a tumor-suppressive environment, thereby aiding in tumor treatment. Better cancer experimental models that mimic the TME such as tumor spheroids, microfluidics, three dimensional (3D) bioprinted models, and organoids will allow deeper investigations of the TME complexity and can lead to the translation of basic tumor biology to effective cancer treatments. Ultimately, innovative cancer treatments and, by extension, improvement in cancer patients' outcomes will emerge from combinatorial drug development strategies targeting both cancer cells and stromal components of the TME. Combinatorial treatment strategies can take the form of chemotherapy and radiotherapy (targeting tumor cells and stromal components) and immunotherapy that is able to regulate immune responses against tumor cells. This expert review thus addresses a previously neglected knowledge gap in cancer drug design and development by broadening the focus in cancer biology to TME so as to empower disruptive health care innovations in the oncology clinic.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/immunology ; Cancer-Associated Fibroblasts/drug effects ; Cancer-Associated Fibroblasts/immunology ; Cancer-Associated Fibroblasts/pathology ; Disease Progression ; Drug Resistance, Neoplasm/immunology ; Extracellular Matrix/drug effects ; Extracellular Matrix/immunology ; Extracellular Matrix/pathology ; Humans ; Immunotherapy/methods ; Lymphatic Metastasis ; Molecular Targeted Therapy/methods ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/pathology ; Organoids/drug effects ; Organoids/immunology ; Organoids/pathology ; Spheroids, Cellular/drug effects ; Spheroids, Cellular/immunology ; Spheroids, Cellular/pathology ; Stromal Cells/drug effects ; Stromal Cells/immunology ; Stromal Cells/pathology ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor
Language	English
Publishing date	2020-03-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2020.0019
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Article ; Online: The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis.

Dzobo, Kevin / Dandara, Collet

Biomimetics (Basel, Switzerland)

2023 Volume 8, Issue 2

Abstract: The extracellular matrix (ECM) is a ubiquitous member of the body and is key to the maintenance of tissue and organ integrity. Initially thought to be a bystander in many cellular processes, the extracellular matrix has been shown to have diverse ... ...

Abstract	The extracellular matrix (ECM) is a ubiquitous member of the body and is key to the maintenance of tissue and organ integrity. Initially thought to be a bystander in many cellular processes, the extracellular matrix has been shown to have diverse components that regulate and activate many cellular processes and ultimately influence cell phenotype. Importantly, the ECM's composition, architecture, and stiffness/elasticity influence cellular phenotypes. Under normal conditions and during development, the synthesized ECM constantly undergoes degradation and remodeling processes via the action of matrix proteases that maintain tissue homeostasis. In many pathological conditions including fibrosis and cancer, ECM synthesis, remodeling, and degradation is dysregulated, causing its integrity to be altered. Both physical and chemical cues from the ECM are sensed via receptors including integrins and play key roles in driving cellular proliferation and differentiation and in the progression of various diseases such as cancers. Advances in 'omics' technologies have seen an increase in studies focusing on bidirectional cell-matrix interactions, and here, we highlight the emerging knowledge on the role played by the ECM during normal development and in pathological conditions. This review summarizes current ECM-targeted therapies that can modify ECM tumors to overcome drug resistance and better cancer treatment.
Language	English
Publishing date	2023-04-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2313-7673
ISSN (online)	2313-7673
DOI	10.3390/biomimetics8020146
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Article ; Online: Epigenomics-Guided Drug Development: Recent Advances in Solving the Cancer Treatment "jigsaw puzzle".

Dzobo, Kevin

Omics : a journal of integrative biology

2019 Volume 23, Issue 2, Page(s) 70–85

Abstract: The human epigenome plays a key role in determining cellular identity and eventually function. Drug discovery undertakings have focused mainly on the role of genomics in carcinogenesis, with the focus turning to the epigenome recently. Drugs targeting ... ...

Abstract	The human epigenome plays a key role in determining cellular identity and eventually function. Drug discovery undertakings have focused mainly on the role of genomics in carcinogenesis, with the focus turning to the epigenome recently. Drugs targeting DNA and histone modifications are under development with some such as 5-azacytidine, decitabine, vorinostat, and panobinostat already approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This expert review offers a critical analysis of the epigenomics-guided drug discovery and development and the opportunities and challenges for the next decade. Importantly, the coupling of epigenetic editing techniques, such as clustered regularly interspersed short palindromic repeat (CRISPR)-CRISPR-associated protein-9 (Cas9) and APOBEC-coupled epigenetic sequencing (ACE-seq) with epigenetic drug screens, will allow the identification of small-molecule inhibitors or drugs able to reverse epigenetic changes responsible for many diseases. In addition, concrete and sustainable innovation in cancer treatment ought to integrate epigenome targeting drugs with classic therapies such as chemotherapy and immunotherapy.
MeSH term(s)	Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; DNA Methylation/genetics ; Epigenesis, Genetic/genetics ; Epigenomics/methods ; Humans
Language	English
Publishing date	2019-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2030312-9
ISSN	1557-8100 ; 1536-2310
ISSN (online)	1557-8100
ISSN	1536-2310
DOI	10.1089/omi.2018.0206
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Article: The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited.

Dzobo, Kevin / Senthebane, Dimakatso A / Dandara, Collet

Cancers

2023 Volume 15, Issue 2

Abstract: Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor ... ...

Abstract	Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis, and highlight various ways through which tumor cells reprogram normal cells into phenotypes that are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to the transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells, including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic, but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to the formation of new vascular networks in order to actively promote and sustain tumor growth via the supply of oxygen and nutrients, whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to the targeting of tumor cells. The reprogramming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centered therapies under investigation.
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15020376
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Article ; Online: Shedding light on the dark genome: Insights into the genetic, CRISPR-based, and pharmacological dependencies of human cancers and disease aggressiveness.

Kafita, Doris / Nkhoma, Panji / Dzobo, Kevin / Sinkala, Musalula

PloS one

2023 Volume 18, Issue 12, Page(s) e0296029

Abstract: Investigating the human genome is vital for identifying risk factors and devising effective therapies to combat genetic disorders and cancer. Despite the extensive knowledge of the "light genome", the poorly understood "dark genome" remains understudied. ...

Abstract	Investigating the human genome is vital for identifying risk factors and devising effective therapies to combat genetic disorders and cancer. Despite the extensive knowledge of the "light genome", the poorly understood "dark genome" remains understudied. In this study, we integrated data from 20,412 protein-coding genes in Pharos and 8,395 patient-derived tumours from The Cancer Genome Atlas (TCGA) to examine the genetic and pharmacological dependencies in human cancers and their treatment implications. We discovered that dark genes exhibited high mutation rates in certain cancers, similar to light genes. By combining the drug response profiles of cancer cells with cell fitness post-CRISPR-mediated gene knockout, we identified the crucial vulnerabilities associated with both dark and light genes. Our analysis also revealed that tumours harbouring dark gene mutations displayed worse overall and disease-free survival rates than those without such mutations. Furthermore, dark gene expression levels significantly influenced patient survival outcomes. Our findings demonstrated a similar distribution of genetic and pharmacological dependencies across the light and dark genomes, suggesting that targeting the dark genome holds promise for cancer treatment. This study underscores the need for ongoing research on the dark genome to better comprehend the underlying mechanisms of cancer and develop more effective therapies.
MeSH term(s)	Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Mutation ; Genome ; Gene Knockout Techniques
Language	English
Publishing date	2023-12-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0296029
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