Pseudoprogression during immunotherapy for gastric adenocarcinoma: A case report and literature review.

Immunotherapy is a novel treatment option for various types of cancers. However, the optimal timing for response evaluation has not been well defined. Here, we present a gastric cancer (GC) patient with microsatellite instability-high who experienced recurrence 5 years and 11 months after radical gastrectomy. Then, the patient was treated with radiotherapy, targeted drugs, and immunotherapy. Immunotherapy resulted in 5 months of continuous progression, accompanied by significantly increased tumor marker CA19-9. However, the patient exhibited a satisfactory response without altering the treatment. Based on this, we hypothesized that some persistent progression with elevated tumor markers, known as pseudoprogression (PsP), might be observed in patients with recurrent GC during immunotherapy. This process might be prolonged, but if the treatment is continued, it will eventually produce remarkable therapeutic effects. PsP might challenge the globally accepted immune response evaluation criteria for solid tumors.

The well-matched interaction between virtuality and reality for intraoperative localization of nonpalpable pulmonary nodules.

Background: The intraoperative localization of nonpalpable pulmonary nodules for thoracoscopic wedge resection is technically challenging. Current preoperative image-guided localization techniques require additional time, costs, procedural risks, advanced facilities, and well-trained operators. In this study, we explored a cost-effective method of well-matched interaction between virtuality and reality for accurate intraoperative localization. Methods: Through the integration of techniques involving preoperative 3-dimensional (3D) reconstruction, temporary clamping of target vessel and the modified inflation-deflation method, the segment on the 3D virtual model and the segment under the thoracoscopic monitor were well matched in the inflated state. Then the spatial relationships of target nodule to the virtual segment could be applied to the actual segment. The well-matched interaction between virtuality and reality would facilitate nodule localization. Results: A total of 53 nodules were successfully localized. The median maximum diameter of the nodules was 9.0 mm (interquartile range [IQR], 7.0-12.5 mm). The median depthmin and depthmax were 10.0 mm and 18.2 mm, respectively. The median macroscopic resection margin was 16 mm (IQR, 7.0-12.5 mm). The median duration of chest tube drainage was 27 hours, with a median total drainage of 170 mL. The median postoperative length of hospital stay was 2 days. Conclusions: The well-matched interaction between virtuality and reality is safe and feasible for intraoperative localization of nonpalpable pulmonary nodules. It may be proposed as a preferred alternative to traditional localization methods.

Division of the intersegmental demarcation using the "modified hand-tearing method" is safe and feasible in thoracoscopic anatomical segmentectomy.

BACKGROUND: The accurate and safe division of the intersegmental demarcation (ISD) is critical and challenging during thoracoscopic anatomical segmentectomy. Here, we provide an improved technique which emphasizes the application of an electric hook and blunt division of ISD. The technique is termed as the "modified hand-tearing method" (MHT method) with combined application of an electric hook and staplers. The study aimed to review the outcomes of patients who underwent thoracoscopic anatomical segmentectomy, with or without the MHT method in our institute and assess its feasibility and safety. In addition, we compared the feasibility between video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracoscopic surgery (RATS) using the MHT method. METHODS: From 2018 July to 2021 June, we retrospectively analyzed 701 patients who underwent segmentectomy. Using propensity score matching, data of two well-matched pairs of 276 cases in the MHT method and non-MHT method groups, and two well-matched pairs of 40 cases in the VATS and RATS subgroups were obtained. The clinical and perioperative characteristics of patients were compared between groups. RESULTS: Compared with the non-MHT method group, the MHT method group had shorter operation time and shorter postoperative hospital stay. Period of chest tube drainage and postoperative total drainage and postoperative complications had no between-group difference. Compared with VATS, the RATS subgroup had less intraoperative bleeding and shorter postoperative hospital stay. CONCLUSION: Division of ISD using the MHT method has advantages in precision and ease of operation, so it has the potential to become a feasible and effective method for thoracoscopic anatomical segmentectomy.

Differential expression of multidrug resistance­related proteins in adriamycin­resistant (pumc­91/ADM) and parental (pumc­91) human bladder cancer cell lines.

Multidrug resistance (MDR) is the major obstacle to bladder cancer chemotherapy. Several mechanisms have been implicated in the development of MDR, including extrusion of the drug by cell membrane pumps, associated with P­glycoprotein (P­gp) and multidrug resistance­associated protein (MRP); increased DNA damage repair, associated with topoisomerase II (Topo II); suppression of drug­induced apoptosis, associated with p53; and regulation of cancer cell growth, associated with vascular endothelial growth factor (VEGF). In the present study, the expression levels of these five markers were detected in an adriamycin (ADM)­resistant human bladder cancer cell line (pumc­91/ADM) and its parental cell line (pumc­91), in order to determine which marker is more important, or whether all of them participate in drug resistance. The expression levels of P­gp, MRP, Topo II, VEGF and p53 were measured in the two cell lines by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemistry. A significant increase in P­gp, MRP and VEGF, and a decrease in Topo II mRNA expression were detected in the pumc­91/ADM drug­resistant cell line compared with the pumc­91 cell line; however, no difference in p53 mRNA expression was detected between the cells. In pumc­91/ADM cells, the protein expression levels of P­gp and MRP were upregulated, whereas Topo II was significantly decreased. However, no marked differences in p53 or VEGF expression were detected between the two cell lines at the protein level. The cytoplasmic and cell membrane localization of P­gp and MRP, the cytoplasmic localization of VEGF, and the nuclear localization of p53 and Topo II were confirmed in the two cell lines. The present study detected increased P­gp and MRP, and reduced Topo II expression in pumc­91/ADM cells compared with pumc­91 cells; however, no difference was detected in p53 and VEGF expression between the cell lines. In conclusion, a significant upregulation of MRP and downregulation of Topo II were detected in the ADM­resistant human bladder cancer cell line (pumc­91/ADM) compared with in the parental cell line (pumc­91).

Correlation of ANXA1 expression with drug resistance and relapse in bladder cancer.

OBJECTIVE: To investigate the expression of annexin a1 (ANXA1) in adriamycin-resistant human bladder cancer cell line (pumc-91/ADM) compared with the parental cell line (pumc-91) and its relevance to the drug resistance of bladder cancer, as well as explore the relevance of ANXA1 in recurrent bladder cancer tissues as pertinent to relapse. METHODS: qRT-PCR and Western blot were implemented to research the level of ANXA1 in two cell lines (pumc-91/ADM and pumc-91). Immunohistochemistry was applied to explore ANXA1 expression in bladder cancer tissues of different intervals of relapse. The association of ANXA1 with clinicopathological parameters was analyzed. RESULTS: The expression of ANXA1 was downregulated in drug-resistant cell line pumc-91/ADM compared to pumc-91. The bladder cancer tissues recurring two years later exhibited higher ANXA1 levels. ANXA1 expression level was positively correlated with T stage, while it was not connected with histological grade strongly. The expression level and influencing factors of ANXA1 in recurrent tissues of bladder cancer were clarified for the first time. CONCLUSION: ANXA1 may become a promising marker to predict the recurrence and drug resistance of bladder cancer and provide guidance for surveillance.

Collection and comparative analysis of 1888 full-length cDNAs from wild rice Oryza rufipogon Griff. W1943.

A huge amount of cDNA and EST resources have been developed for cultivated rice species Oryza sativa; however, only few cDNA resources are available for wild rice species. In this study, we isolated and completely sequenced 1888 putative full-length cDNA (FLcDNA) clones from wild rice Oryza rufipogon Griff. W1943 for comparative analysis between wild and cultivated rice species. Two cDNA libraries were constructed from 3-week-old leaf samples under either normal or cold-treated conditions. Homology searching of these cDNA sequences revealed that >96.8% of the wild rice cDNAs were matched to the cultivated rice O. sativa ssp. japonica cv. Nipponbare genome sequence. However, <22% of them were fully matched to the cv. Nipponbare genome sequence. The comparative analysis showed that O. rufipogon W1943 had greater similarity to O. sativa ssp. japonica than to ssp. indica cultivars. In addition, 17 novel rice cDNAs were identified, and 41 putative tissue-specific expression genes were defined through searching the rice massively parallel signature-sequencing database. In conclusion, these FLcDNA clones are a resource for further function verification and could be broadly utilized in rice biological studies.

A collection of 10,096 indica rice full-length cDNAs reveals highly expressed sequence divergence between Oryza sativa indica and japonica subspecies.

Relatively few indica rice full-length cDNAs were available to aid in the annotation of rice genes. The data presented here described the sequencing and analysis of 10,096 full-length cDNAs from Oryza sativa subspecies indica Guangluai 4. Of them, 9,029 matched rice genomic sequences in publicly-available databases, and 1,200 were identified as new rice genes. Comparison with the knowledge-based Oryza Molecular Biological Encyclopedia japonica cDNA collection indicated that 3,316 (41.6%) of the 7,965 indica-japonica cDNA pairs showed no distinct variations at protein level (2,117 indica-japonica cDNA pairs showed fully identical and 1,199 indica-japonica cDNA pairs showed no frame shift). Moreover, 3,645 (45.8%) of the indica-japonica pairs showed substantial differences at the protein level due to single nucleotide polymorphisms (SNPs), insertions or deletions, and sequence-segment variations between indica and japonica subspecies. Further experimental verifications using PCR screening and quantitative reverse transcriptional PCR revealed unique transcripts for indica subspecies. Comparative analysis also showed that most of rice genes were evolved under purifying selection. These variations might distinguish the phenotypic changes of the two cultivated rice subspecies indica and japonica. Analysis of these cDNAs extends known rice genes and identifies new ones in rice.

A tiling microarray expression analysis of rice chromosome 4 suggests a chromosome-level regulation of transcription.

The complete genome sequence of cultivated rice (Oryza sativa) provides an unprecedented opportunity to understand the biology of this model cereal. An essential and necessary step in this effort is the determination of the coding information and expression patterns of each sequenced chromosome. Here, we report an analysis of the transcriptional activity of rice chromosome 4 using a tiling path microarray based on PCR-generated genomic DNA fragments. Six representative rice organ types were examined using this microarray to catalog the transcribed regions of rice chromosome 4 and to reveal organ- and developmental stage-specific transcription patterns. This analysis provided expression support for 82% of the gene models in the chromosome. Transcriptional activities in 1643 nonannotated regions were also detected. Comparison with cytologically defined chromatin features indicated that in juvenile-stage rice the euchromatic region is more actively transcribed than is the transposon-rich heterochromatic portion of the chromosome. Interestingly, increased transcription of transposon-related gene models in certain heterochromatic regions was observed in mature-stage rice organs and in suspension-cultured cells. These results suggest a close correlation between transcriptional activity and chromosome organization and the developmental regulation of transcription activity at the chromosome level.

Sequence and analysis of rice chromosome 4.

Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.

A fine physical map of the rice chromosome 4.

As part of an international effort to completely sequence the rice genome, we have produced a fine bacterial artificial chromosome (BAC)-based physical map of the Oryza sativa japonica Nipponbare chromosome 4 through an integration of 114 sequenced BAC clones from a taxonomically related subspecies O. sativa indica Guangluai 4 and 182 RFLP and 407 expressed sequence tag (EST) markers with the fingerprinted data of the Nipponbare genome. The map consists of 11 contigs with a total length of 34.5 Mb covering 94% of the estimated chromosome size (36.8 Mb). BAC clones corresponding to telomeres, as well as to the centromere position, were determined by BAC-pachytene chromosome fluorescence in situ hybridization (FISH). This gave rise to an estimated length ratio of 5.13 for the long arm and 2.9 for the short arm (on the basis of the physical map), which indicates that the short arm is a highly condensed one. The FISH analysis and physical mapping also showed that the short arm and the pericentromeric region of the long arm are rich in heterochromatin, which occupied 45% of the chromosome, indicating that this chromosome is likely very difficult to sequence. To our knowledge, this map provides the first example of a rapid and reliable physical mapping on the basis of the integration of the data from two taxonomically related subspecies.