Personalized medicine of non-gene-specific chemotherapies for non-small cell lung cancer

Non-small cell lung cancer is recognized as the deadliest cancer across the globe. In some areas, it is more common in women than even breast and cervical cancer. Its rise, vaulted by smoking habits and increasing air pollution, has garnered much attention and resource in the medical field. The first lung cancer treatments were developed more than half a century ago. Unfortunately, many of the earlier chemotherapies often did more harm than good, especially when they were used to treat genetically unsuitable patients. With the introduction of personalized medicine, physicians are increasingly aware of when, how, and in whom, to use certain anti-cancer agents. Drugs such as tyrosine kinase inhibitors, anaplastic lymphoma kinase inhibitors, and monoclonal antibodies possess limited utility because they target specific oncogenic mutations, but other drugs that target mechanisms universal to all cancers do not. In this review, we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors (

Personalized medicine in non-small cell lung cancer: a review from a pharmacogenomics perspective

Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, the cornerstone of personalized medicine using genetic profiling to direct treatment has exalted the successes seen in the field and raised the standard for patient treatment in lung and other cancers. Here, we discuss the current state and advances in the field of personalized medicine for lung cancer, reviewing several of the mutation-targeting strategies that are approved for clinical use and how they are guided by patient genetic information. These classes include inhibitors of tyrosine kinase (TKI), anaplastic lymphoma kinase (ALK), and monoclonal antibodies. Selecting from these treatment plans and determining the optimal dosage requires in-depth genetic guidance with consideration towards not only the underlying target genes but also other factors such as individual metabolic capability and presence of resistance-conferring mutations both directly on the target gene and along its cascade(s). Finally, we provide our viewpoints on the future of personalized medicine in lung cancer, including target-based drug combination, mutation-guided drug design and the necessity for data of population genetics, to provide rough guidance on treating patients who are unable to get genetic testing.

Strategy of Conclusion-Making for Paternity Testing with Short Tandem Repeats Genotyping / 中山大学学报(医学科学版)

[Objective] To propose a criterion for making conclusions on paternity tests based on STR genotyping. [Method] To use binomial distribution formula to calculate minimal numbers of STR loci that must be tested for different scenarios in paternity testing. [ Results ] We proposed a set of criteria for making STR paternity testing conclusions. For triplet tests, concluded "paternity positive" for the following four cases when the cumulative paternity index (PI) was greater than 10 000: 1) no inconsistent STR locus was detected in 15 loci (PE > 0.571 4/locus) or 2) only one inconsistent STR locus was detected in 19 loci or 3) only two inconsistent STR loci were detected in 28 loci or 4) only three inconsistent STR loci were detected in 35 loci; otherwise, concluded "paternity negative" when at least four inconsistent STR loci had been detected. For single parent tests, concluded "paternity non-exclusive" for the following cases when the cumulative PI was greater than 10 000: 1) no inconsistent STR locus was detected in 18 loci (PE>0.411/locus) or 2) only one inconsistent STR locus was detected in 29 loci or 3) two inconsistent STR loci were detected in 41 loci; concluded "paternity negative" when three or more inconsistent loci were detected. [Conclusion] Our experience has proven that these criteria are robust in STR paternity testing.

Linkage analysis of susceptibility genes for familial schizophrenia on chromosome 1 in Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the molecular genetic relationship between chromosome 1 and susceptibility genes for familial schizophrenia in Chinese population.</p><p><b>METHODS</b>A genome scanning was conducted in 32 multiplex pedigrees from Chinese population by using 29 microsatellite markers on chromosome 1.</p><p><b>RESULTS</b>Multipoint parametric analysis detected a maximum heterogenicity Lod of 1.70 at 262.52 cM under a recessive model; multipoint non-parametric analysis detected a maximum non-parameter linkage (NPL) of 1.71 (P=0.046) at 262.52 cM, then 1.37 (P=0.086) at 149.70 cM, corresponding to marker D1S206 and D1S425 respectively.</p><p><b>CONCLUSION</b>These results give further supports to the presence of susceptibility genes on chromosome 1q for familial schizophrenia.</p>

Linkage disequilibrium study of microsatellite markers on chromosome 6 and schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the microsatellite markers on chromosome 6 and schizophrenia by linkage disequilibrium analysis.</p><p><b>METHODS</b>Twenty-eight microsatellite markers on chromosome 6 were evaluated in 115 affected-sib-pair and trios families. Linkage disequilibrium analysis was conducted according to diagnostic categories, Positive and Negative Syndrome Scale (PANSS) and other clinical data by XDT and MAPMAKER/SIBS software system.</p><p><b>RESULTS</b>Significant P value (P<0.005) was found in all the four diagnostic categories. Only the locus of D6S1960 showed positive P value (P<0.05) in all the subgroups divided by PANSS scale and the age of onset.</p><p><b>CONCLUSION</b>The area around D6S1960 in short arm of chromosome 6 may contain susceptibility gene of schizophrenia.</p>

A linkage disequilibrium study of methylenetetrahydrofolate reductase C677T and schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the methylenetetrahy drofolate reductase (MTHFR) C677T missense mutation and schizophrenia by linkage disequilibrium study.</p><p><b>METHODS</b>Linkage disequilibrium analys is was conducted bet ween MTHFR C677T and schizophrenia in 115 affected-sib-pair (105) and trios (10) families by XDT and MAPMAKER/SIBS soft system. The analyses were performed in different diagnostic categories and combined with the age of onset as well.</p><p><b>RESULTS</b>No positive results were found in the analysis in all the family in all the four diagnostic categories. Significant P values, which were P<0.05, P<0.01 respectively, were observed in the families with the affected individual's onset age less than 25 years in all the four diagnostic categories.</p><p><b>CONCLUSION</b>The missense mutation of MTHFR C677T or other gene structure around this mutation may be one of the susceptibility gene of schizophrenia.</p>

A linkage analysis of quantitative trait loci for familial schizophrenia on chromosome 1 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the molecular genetic relationship between chromosome 1 and quantitative trait loci for familial schizophrenia.</p><p><b>METHODS</b>A series of assessment scales included positive and negative syndrome scale (PANSS), global assessment of functional scale (GAFS), premorbid schizoid and schizotypal traits scale (PSST), premorbid social adjustment scale (PSA) were applied to quantify the phenotypes of schizophrenia. Non-parametric linkage analysis of quantitative traits was conducted in 32 multiplex pedigrees with schizophrenia by using 29 microsatellite makers on chromosome 1.</p><p><b>RESULTS</b>Haseman-Elston quantitative trait analysis detected a maximum Traditional H-E Lods of 1.73 and a maximum EH H-E Lods of 1.65 of negative symptoms (PANSS-N ) at 147.64 cM, which was overlapped to the positive region of 1q21-23 in qualitative linkage analysis.</p><p><b>CONCLUSION</b>The results suggest there might be an independent quantitative trait locus of negative symptoms on 1q21-23 for familial schizophrenia.</p>

Mechanisms of orindonin induced apoptosis on NB_4 cells / 中成药

Objective: To explore the mechanism of orindonin induced apoptosis on NB4 (Human acute promylocytic leukeamia cell line) cells. Methods: The variation of both morphology and inhibitory rate of NB4 cells were observed in culture medium with various concentrations of orindonin at different time in vitro. The activity of Caspase3 was detected before and after apoptosis occurred. Results: orindonin could increase the activity of Caspase3, inhibit the growth and cause apoptosis on NB4 cells significantly. The variations were both in time and dose dependent manner. Conclusion: Orindonin can inhibit the growth of NB4 cells and induce apoptosis. Increasing the activity of Caspase3 may be one of the most important mechanism.