Tumor heterogeneity and drug resistance.

1986 ◽  
Vol 4 (2) ◽  
pp. 244-257 ◽  
Author(s):  
D L Dexter ◽  
J T Leith
Keyword(s):  
Drug Resistance ◽  
Tumor Heterogeneity ◽  
Metastatic Potential ◽  
Primary Tumors ◽  
Multiple Tumor ◽  
Underlying Basis ◽  
Human Solid Tumors ◽  
History Of ◽  
Relationship Of ◽  
The Impact

Drug resistance has long been identified as a major reason for therapy failure in cancer patients. Concurrently, work from many laboratories in the past 10 years has established tumor heterogeneity as a phenomenon of critical importance in the natural history of individual neoplasms. The two most sinister aspects of intraneoplastic diversity in human solid tumors are the genesis of clones with metastatic potential, and the existence of drug-resistant variants in primary cancers and their metastases. Thus, recent investigations on drug resistance and on tumor heterogeneity have converged to focus attention on the clonal organization of primary tumors and their metastases as the underlying basis for anticancer drug resistance. This review examines the degree of heterogeneity observed within tumors and the relationship of this diversity to resistance that might be anticipated for any given agent. A question critical to our discussion is "How many subpopulations are there?" The impact of multiple tumor clones on therapy is next discussed in relationship to normal tissue tolerance, the barrier clinicians face regardless of the specific agent used in treatment. Finally, laboratory and clinical approaches are presented for addressing a drug resistance problem that is seemingly overwhelming because of its complex biological roots.

Gene mutation and drug resistance of M. tuberculosis in the patients followed up in the city of Moscow

2020 ◽  
Vol 97 (12) ◽  
pp. 34-44
Author(s):  
M. A. Krasnova ◽  
E. M. Belilovsky ◽  
S. E. Borisov ◽  
A. A. Khakhalina ◽  
Yu. D. Mikhaylova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Statistical Significance ◽  
Molecular Genetic ◽  
Previous Treatment ◽  
Repeated Treatment ◽  
Phenotypic Resistance ◽  
Therapy Regimen ◽  
Treatment History ◽  
History Of ◽  
Relationship Of

The article describes a retrospective study of the results of microbiological and molecular genetic tests of 685 M. tuberculosis cultures isolated from 685 adult tuberculosis patients registered for dispensary follow-up in Moscow in 2014.The following was identified during the study: phenotypic drug resistance (FDR) of MTB to rifampicin, isoniazid, fluoroquinolones, kanamycin, amikacin, and capreomycin in groups of patients with different treatment history; the frequency of FDR to the above anti-tuberculosis drugs in strains with mutations being drug resistance markers; the frequency of various mutations in case of FDR of mycobacteria in the patients from different groups; the relationship of FDR or the presence of a particular mutation with various characteristics of the patients and their treatment history.The history of previous treatment was determined as statistical significance to provide the greatest influence on the spread of drug resistant MTB: patients undergoing repeated treatment had FDR more often and also a much more pronounced variety of mutations being markers of FDR to certain anti-tuberculosis drugs.The results of the study showed that the detection of genetic mutations in MBT associated with FDR was a reliable tool for predicting phenotypic resistance and should be used as the main method for selecting anti-tuberculosis drugs when compiling the etiotropic therapy regimen.

The Economic History of South Africa 1948–94

2021 ◽  
pp. 46-65
Author(s):  
Bill Freund ◽  
Vishnu Padayachee
Keyword(s):  
Economic Growth ◽  
South Africa ◽  
South African ◽  
Economic History ◽  
History Of ◽  
Anglo American ◽  
Relationship Of ◽  
Global And Local ◽  
The Impact ◽  
The Way

This chapter addresses the unfolding economic history of South Africa in the apartheid era (1948–94). The chapter is organized according to a periodization with 1971–73 as a marker of the break, and along specific thematic lines. These include a discussion of the way in which this history has been studied and through what theoretical lenses, before engaging with the main issues, including the impact of Afrikaner nationalism on economic growth, the way in which the minerals energy sector, which dominated early perspectives of South African economic history and perspectives, is impacted in this era of National Party rule. An analysis of the role of one major corporation (Anglo American Corporation) in shaping this economic history is followed by an assessment of the impact of the global and local crisis after c.1970 on the South African economy. An abiding theme is that of race and economic development and the way in which the impact of this key relationship of apartheid South Africa on economic growth has been studied.

Childhood maltreatment modifies the relationship of depression with hippocampal volume

2015 ◽  
Vol 45 (16) ◽  
pp. 3517-3526 ◽  
Author(s):  
L. Gerritsen ◽  
L. van Velzen ◽  
L. Schmaal ◽  
Y. van der Graaf ◽  
N. van der Wee ◽  
...  
Keyword(s):  
Childhood Maltreatment ◽  
Hippocampal Volume ◽  
Diagnostic Interview ◽  
Analysis Of Covariance ◽  
Intracranial Volume ◽  
Mr Images ◽  
History Of ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Background.Childhood maltreatment (CM) may modify the relationship between major depressive disorder (MDD) and hippocampal volume reduction. To disentangle the impact of MDD and CM on hippocampal volume we investigated the association between MDD and hippocampal volume in persons with and without a history of CM in two independent cohorts.Method.We used data of 262 participants from the Netherlands Study of Depression and Anxiety (NESDA) (mean age 37 years, 32% male) and 636 participants from the SMART-Medea study (mean age 61 years, 81% male). In both studies a 12-month diagnosis of MDD and CM were assessed using a diagnostic interview. Hippocampal volume was measured in NESDA using FreeSurfer software on 3-T magnetic resonance (MR) images and in SMART it was manually outlined on 1.5-T MR images. With analysis of covariance adjusted for intracranial volume, age, gender and lifestyle factors we estimated the effects of MDD and CM on hippocampal volume.Results.In both cohorts CM was not significantly associated with hippocampal volume. After pooling the data MDD was associated with smaller hippocampal volume (B = −138.90 mm3, p = 0.05) and the interaction between MDD and CM reached significance (p = 0.04); in participants with CM, MDD was related to smaller hippocampal volume (NESDA: B = −316.8 mm3, p = 0.02; SMART: B = −407.6, p = 0.046), but not in participants without CM (p > 0.05).Conclusions.Our study shows that in two independent cohorts, particularly in individuals with CM, a diagnosis of MDD is related to smaller hippocampal volume. Prospective studies are needed to further determine through which mechanism CM may amplify the relationship between MDD and hippocampal volume.

scholarly journals Tumor Heterogeneity: A Great Barrier in the Age of Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 806 ◽  
Author(s):  
Nader El-Sayes ◽  
Alyssa Vito ◽  
Karen Mossman
Keyword(s):  
Cancer Immunotherapy ◽  
Tumor Heterogeneity ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Intrinsic Resistance ◽  
Treatment Regimens ◽  
Hypoxic Conditions ◽  
Oncology Research ◽  
History Of ◽  
The Impact

Throughout the history of oncology research, tumor heterogeneity has been a major hurdle for the successful treatment of cancer. As a result of aberrant changes in the tumor microenvironment such as high mutational burden, hypoxic conditions and abnormal vasculature, several malignant subpopulations often exist within a single tumor mass. Therapeutic intervention can also increase selective pressure towards subpopulations with acquired resistance. This phenomenon is often the cause of relapse in previously responsive patients, drastically changing the expected outcome of therapy. In the case of cancer immunotherapy, tumor heterogeneity is a substantial barrier as acquired resistance often takes the form of antigen escape and immunosuppression. In an effort to combat intrinsic resistance mechanisms, therapies are often combined as a multi-pronged approach to target multiple pathways simultaneously. These multi-therapy regimens have long been a mainstay of clinical oncology with chemotherapy cocktails but are more recently being investigated in the emerging landscape of immunotherapy. Furthermore, as high throughput technology becomes more affordable and accessible, researchers continue to deepen their understanding of the factors that influence tumor heterogeneity and shape the TME over the course of treatment regimens. In this review, we will investigate the factors that give rise to tumor heterogeneity and the impact it has on the field of immunotherapy. We will discuss how tumor heterogeneity causes resistance to various treatments and review the strategies currently being employed to overcome this challenging clinical hurdle. Finally, we will outline areas of research that should be prioritized to gain a better understanding of tumor heterogeneity and develop appropriate solutions.

scholarly journals Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains

2020 ◽  
Author(s):  
Yongjian Liu ◽  
Yu Zhang ◽  
Hanping Li ◽  
Xiaolin Wang ◽  
Lei Jia ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Geographic Distance ◽  
Sequence Database ◽  
Genotypic Resistance ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
Treatment Naïve ◽  
Relationship Of ◽  
The Impact ◽  
Search Program ◽  
Hiv 1

Abstract Background: There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance. Methods: We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database. Results: A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients. Conclusions: This study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.

Problems in the Relationship of Communication and Economic History

1960 ◽  
Vol 20 (4) ◽  
pp. 559-565 ◽  
Author(s):  
W. T. Easterbrook
Keyword(s):  
Economic History ◽  
Historical Analysis ◽  
Communication Research ◽  
Physical Sciences ◽  
The Social ◽  
Major Break ◽  
History Of ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Present interest in communication research in the social and physical sciences raises some interesting and difficult questions for the economic historian. Arthur Cole, who claims that he is merely trying to carry further the work of Harold Innis and others at Toronto, but who is surely the moving spirit in this session, has suggested that we might begin by pin-pointing a few leading questions for examination. Is this comparatively recent development to be regarded as merely a passing phase in the history of fashions in thought? Is the process of relating communication to economic change mainly a process of sophistication and is there anything to argue about in this relationship? Or, on the other hand, does it in fact amount to a major break-through in scientific and historical analysis, something comparable to the impact made on economics about a century ago by the Austrian School?

Mande

2020 ◽  
pp. 173-183
Author(s):  
Henning Schreiber
Keyword(s):  
Linguistic Data ◽  
Phylogenetic Methods ◽  
Genealogical Relationship ◽  
Theoretical Assumptions ◽  
History Of ◽  
Linguistic Classification ◽  
Methodological Aspects ◽  
Relationship Of ◽  
The Impact

The chapter surveys the history of classification of Mande languages from the first attempts in 1849 to the most recent ones on the basis of quantitative approaches to language classification, linguistic reconstruction, and theories on language stability. It discusses various proposals for the internal genealogical relationship of Mande languages and examines their advances and differences in the light of methodological aspects and availability of reliable linguistic data. Special emphasis is laid on the historical tan/fu dichotomy and its revision. Typological issues are treated in the discussion of Mande-specific typological obstacles for lexicostatistic classification. The problem of internal convergence for the linguistic classification of Mande is exemplified in particular in accounting the impact of Greater Manding. The effect of changes in classification methodology by the introduction of phylogenetic methods and theoretical assumptions about language stability are addressed in the final discussion of a revised classification of Mande.

“Tout comprendre, c’est tout pardonner?” The “Case of Jauss”

2017 ◽  
Vol 2 (3-4) ◽  
pp. 388-402
Author(s):  
Ottmar Ette
Keyword(s):  
Aesthetic Experience ◽  
World View ◽  
Rational Form ◽  
History Of ◽  
Style Of Thought ◽  
Ästhetische Erfahrung ◽  
Reader Response Criticism ◽  
Relationship Of ◽  
The Impact ◽  
Triadic Relationship

Hans Robert Jauss cannot simply be excluded from the history of Romance Studies, or from the history of literary science in 20th century Germany: the attractive power of his style of thought, writing and scholarship was too profound, his machine de guerre too powerful. If the “case of Jauss” is now on its way to becoming the “paradigm of Jauss,” it is time to examine scientifically the text and work, the impact and the reception of the author of Ästhetische Erfahrung und literarische Hermeneutik (“Aesthetic Experience and Literary Hermeneutics”), and to illuminate them from the perspective of Romance Studies. The considerations put forth in this essay should in no way diminish the undeniable merits of the founder of “Reader-response criticism”. With him and with his words, one may surely hold on to the hope that “the triadic relationship of technology, communication, and world view” can be brought “once more into equilibrium.” Hans Robert Jauss—to use the words of Jorge Semprún—traveled the very short, and at the same time very long, path from Buchenwald to Weimar: a path that first led him into the most abysmal, reprehensible, and rational form of human barbarism, which he wished to leave behind him as quickly as possible after the end of the war. His path to Weimar, as the symbol of a “refined” western culture, was extremely short: indeed, all too short.

scholarly journals The impact of fast radiation on the phylogeny of Bactrocera fruit flies

2021 ◽  
Author(s):  
Federica Valerio ◽  
Nicola Zadra ◽  
Omar Rota Stabelli ◽  
Lino Ometto
Keyword(s):  
Incomplete Lineage Sorting ◽  
Fruit Flies ◽  
Lineage Sorting ◽  
Genomic Dataset ◽  
History Of ◽  
Approaches To Study ◽  
Phylogenetic Framework ◽  
Relationship Of ◽  
The Impact ◽  
Relaxed Clock

AbstractTrue fruit flies (Tephritidae) include several species that cause extensive damage to agriculture worldwide. Among them, species of the genus Bactrocera are widely studied to understand the traits associated to their invasiveness and ecology. Comparative approaches based on a reliable phylogenetic framework are particularly effective, but, to date, molecular phylogenies of Bactrocera are still controversial. Here, we employed a comprehensive genomic dataset to infer a robust backbone phylogeny of eleven representative Bactrocera species and two outgroups. We further provide the first genome scaled inference of their divergence using calibrated relaxed clock. The results of our analyses support a closer relationship of B. dorsalis to B. latifrons than to B. tryoni, in contrast to all mitochondrial-based phylogenies. By comparing different evolutionary models, we show that this incongruence likely derives from the fast and recent radiation of these species that occurred around 2 million years ago, which may be associated with incomplete lineage sorting and possibly (ongoing) hybridization. These results can serve as basis for future comparative analyses and highlight the utility of using large datasets and efficient phylogenetic approaches to study the evolutionary history of species of economic importance.

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