A Winning New Combination? Toward Clinical Application in Oncology.

Immunotherapy has substantial attention in oncology due to the success of CTLA-4 and PD-1 inhibitors in the treatment of melanoma, lung cancer, head and neck cancer, renal cell carcinoma, and Hodgkin's lymphoma. A deeper understanding of interaction of tumor with its environment and the immune system provides best guide for oncology research. Recent studies in oncology have explained how a tumor alters antigen presentation, avoids detection, and activation of the host immune system to live and develop. Understanding the connections between the tumor and the immune system has resulted in several innovative therapy options. The extensive field of gene therapy has provided a number of cutting-edge medicines that are expected to play an important role in lowering cancer-related mortality. This article explains the history, important breakthroughs, and future prospects for three separate gene therapy treatment modalities: immunotherapy, oncolytic virotherapy, and gene transfer. Immunotherapies have completely changed how cancer is treated, especially for individuals whose condition was previously thought to be incurable. Examples include ACT (adoptive cell therapy) and ICB (immune checkpoint blockade). This review article will discuss the relationship between the immune response to cancer and the mechanisms of immunotherapy resistance. It will cover combination drugs authorized by the US Food and Drug Administration and provide a thorough overview of how these drugs are doing clinically right now. Cytokines, vaccines, and other soluble immunoregulatory agents, innate immune modifiers, ACT, virotherapy, and other treatment modalities will all be covered in detail.

Forensic and phylogenetic characterization of 15 autosomal STRs in Hazara population of Pakistan.

In the current study, 217 unrelated individuals of the Hazara population were genotyped for 15 autosomal short tandem repeats to generate parentage and forensic efficacy parameters. Hazaras belong to the Shi'a sect and are recognized by their Turko-Mogholi features. We found that D2S1338 was the most discriminatory locus with a maximum power of exclusion and high value of polymorphism information content. Whilst the Combined Power of Discrimination (CPD), Combined Matching Probability (CMP) and Combined Power of Exclusion (CPE) were 0.999999999999999, 2.76796338879E-17 and 0.999999040733479 respectively. Furthermore, the pattern of genetic affinity with genetically assumed related populations was demonstrated through Heat Map and Phylogenetic analysis, which revealed a great level of genetic closeness of Hazaras with Mongol population and descendants of Genghis Khan. The resulting data can be used for forensic applications and anthropological studies.

Population genetic data of 30 insertion-deletion markers in Punjabi population of Pakistan.

Insertion-deletion polymorphism (Indels) is valuable diallelic markers for forensic as well as parentage analysis. The Investigator DIPplex Kit (Qiagen) contains thirty autosomal Indels markers along with amelogenin. These thirty markers were tested in the Pakistani Punjabi Population but no significant deviations were observed from Hardy-Weinberg equilibrium rule expectations (Bonferroni corrected) except HLD58, HLD56, HLD99, and HLD40. The mean expected and observed heterozygosity was found 0.4701 and 0.4667 respectively; combined matching probability was computed as 7.31867 × 10-13. However, the use of the 30 Indels markers proved to be a good supplementary tool in forensic casework, particularly when evidence sample is highly degraded. The significant genetic differences were also observed between the Punjabi and other populations of the world.

Kashmiris phylogenetic depictions through uniparental and biparental genetic markers.

In this study, the Kashmiri population was genetically screened for fifteen autosomal STRs, seventeen Y-chromosomal STRs and mitochondrial DNA control region SNPs. Autosomal STRs exhibited that D2S1338 was the most discriminatory locus with value of 0.963 whereas combine power of discrimination was 0.999999999999999. On the other hand, analysis of Y-chromosomal STRs generated 59 distinct haplotypes of which 52 were unique with haplotype diversity value of 0.99752. Mitochondrial D-loop analysis resulted that haplogroups M and U were found most prevalent with 25% each. Haplotypic data of Y-STRs was submitted to YHRD under accession number YA004153 whereas mitochondrial DNA control region (CR) sequences were submitted to EMPOP with accession number EMP00683.

Genetic polymorphism of 15 autosomal short tandem repeats in Baloch population of Pakistan.

Allele frequencies and forensic statistical parameters of 15 autosomal short tandem repeats (STRs) were evaluated in 200 genetically unrelated individuals of the Baloch population of Pakistan. Total 155 alleles were observed with allele frequencies ranged from 0.003 to 0.425. Among the 15 STRs, D2S1338 was found to be the most polymorphic and discriminating locus while TPOX was the least polymorphic and discriminating locus. The combined power of discrimination (CPD), combined power of exclusion (CPE), and combined matching probability (CMP) were found to be 0.9999999999999999978, 0.999994252, and 2.14012 × 10-18, respectively. No significant deviation from Hardy-Weinberg Equilibrium (HWE) was observed except for locus D21S11. Additionally, a correlation between previously published data and Baloch population is also presented.

Genetic analysis of 15 autosomal STRs in Yousafzai population of Pakistan.

Yousafzai is a Pushto-speaking Pathan tribe inhabiting the northern province of Pakistan who claim to be descendants of the prophet Yousaf (Joseph). Forensic and genetic parameters were determined for 203 genetically unrelated individuals on 15 autosomal STRs. D2S1338 was the most discriminating locus whereas TPOX was the least. The combined matching probability (CMP) for all loci was 1.52458 × 10-18 while combined power of discrimination (CPD) and combined power of exclusion (CPE) was 0.9999999999999999984 and 0.999998628, respectively. The Yousafzai population was in Hardy-Weinberg equilibrium after Bonferroni correction except for loci D3S1358 and D19S433. Pairwise genetic distance analysis was carried out by comparing with various populations at local and global levels. The findings of this study are valuable for population genetics and forensics analysis.

SE33 locus as a reliable genetic marker for forensic DNA analysis systems

Background/aim: Genetic variation, an authentic tool of individual discrimination, is being used for forensic investigations worldwide. A missing result for even one out of 13-17 markers leads to an inconclusive report. Additional reliable markers are required to compensate such deficiencies. The SE33 locus has high genetic variability in different populations and is being used in forensic investigation systems in some countries. The purpose of the study was to assess the viability of use of the SE33 locus as a supportive marker for forensic DNA profiling. Materials and methods: Amplification of the SE33 locus was performed using the PowerPlex ES Monoplex System SE33 (Promega). After genotyping 204 Pakistani individuals, different genetic and forensic parameters for the SE33 locus were studied. Results: Genotyping of the SE33 locus revealed a total of 43 alleles including 3 novel alleles. Significant values of different forensic and genetic parameters including power of discrimination, power of exclusion, and polymorphism information content were observed. Conclusions: Addition of the SE33 locus in forensic DNA profiling may help to produce conclusive reports where results are inconclusive due to degraded evidence samples. The SE33 locus can confidently be used for Pakistani and neighboring populations having common ancestors from Iran to Central Asia, the Middle East, India and Turkey.

Genetic variations of 15 autosomal and 17 Y-STR markers in Sindhi population of Pakistan.

This study comprises genetic characterization of 15 autosomal and 17 Y-chromosomal STR loci in 103 unrelated male inhabitants of the Sindhi population to establish its lineage and parameters of forensic interest. The examined autosomal STRs revealed high combined power of discrimination, combined power of exclusion, and the combined matching probability as 0.99999999999999999042580, 0.9999977141, and 9.5742 × 10-18, respectively. A total of 89 unique haplotypes were obtained, of which 84 were observed once with a haplotype diversity value of 0.999677. The resulted Y-STR haplotypes exhibited a high degree of geographical demarcation by comparing with other populations at the local and global levels.

Development of new PCR multiplex system by the simultaneous detection of 10 miniSTRs, SE33, Penta E, Penta D, and four Y-STRs.

The 18 loci multiplex system has been instigated for co-amplification and fluorescent detection of Amelogenin and 17 STRs, including 10 MiniSTRs (CSF1PO, D18S51, D7S820, D2S1338, TPOX, D13S317, FGA, D5S818, D21S11, D16S539), SE33, Penta E, Penta D, and four Y-STRs (DYS385a/b, DYS438, DYS392). This multiplex system was developed for the simultaneous analysis of compromised DNA samples, Y-amelogenin marker mutation, motherless paternity issues where single allele sharing occurs at autosomal STRs in unrelated individuals, and other complex forensic cases. Selection of loci, primers, and allelic ladders were designed and created in-house with a design strategy to work in this multiplex. The multiplex system was evaluated by sensitivity, specificity, stability, precision and accuracy, case-type samples, mixture studies, PCR-based and population distribution studies to establish the robustness and reliability of the system as the current requirements of the forensic case work. Among all the markers evaluated for this study, 209 alleles including 44 variants were observed with combined power of discrimination, combined power of exclusion, and the combined probability of matching calculated as 0.999999999999999999893916339344, 0.999993816173890, and 5.90019 × 10-19, respectively. Due to highly polymorphic characteristics of these loci particularly SE33 and Penta E which are most discriminatory (PD = 0.991 and 0.983, respectively) in the Pakistani population, this multiplex would be highly valuable for individual identification in complex forensic cases and paternity issues as well as population database.

Genetic distribution of 15 autosomal STR markers in the Punjabi population of Pakistan.

Genetic diversity of 15 autosomal short tandem repeat (STR) loci was evaluated in 713 unrelated individual samples of a Punjabi population of Pakistan. These loci were scrutinized to establish allelic frequencies and statistical parameters of forensic and paternity interests. A total of 165 alleles were observed with the corresponding allele frequencies ranging from 0.001 to 0.446. D2S1338 was found as the most informative locus while TPOX (0.611) was the least discriminating locus. The combined power of discrimination (CPD), the combined probability of exclusion (CPE), and cumulative probability of matching (CPM) were found equaled to 0.999999999999999998606227424808, 0.999995777557989, and 1.37543 × 10-18, respectively. All the loci followed the Hardy-Weinberg equilibrium after the Bonferroni correction (p < 0.0033) except one locus D3S1358. The study revealed that these STR loci are highly polymorphic, suitable for forensic and parentage analyses. In comparison to different populations (Asians and non-Asians), significant differences were recorded for these loci.

The tribe Scymnini (Coccinellidae: Coleoptera) from Sindh Province, Pakistan.

Coccinellids are important natural enemies of aphids, scale insects, mealybugs, whiteflies, jassids and mites. They are being augmented or conserved for population reduction of different agricultural crop pests in the concept of Integrated Pest Management throughout the world. The genera and species in the tribe Scymnini known from Pakistan are revised and redescribed. Two genera including two subgenera and six species among which three species are newly reported, is therefore, a new addition to Coccinellid fauna of Pakistan. Keys to all taxa, descriptions of the higher taxa, species diagnoses, synonymies, and distribution records are included.