Efficacy and safety of pembrolizumab monotherapy in EGFR-mutant squamous cell lung cancer with PD-L1 over-expression: A case report.

BACKGROUND: Epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) patients are less likely to be programmed death-ligand 1 (PD-L1)-positive compared with wild-type EGFR mutant tumors. Given the rarity of actionable driver genes in squamous cell lung cancer (SQCC), the frequency of SQCC patients simultaneously carrying EGFR driver gene mutation and having PD-L1 over-expression is extremely low. Studies on the effectiveness and safety of EGFR-TKIs or immune-checkpoint inhibitors (ICIs) in this subset of patients are lacking. PATIENT CONCERNS: The patient suffered from coughing and chest pain for 1 month. A chest CT revealed a mass with a cavity in the right lung, enlarged mediastinal lymph nodes, diffuse pleural thickening in the right pleura, and pleural effusion of the right chest. DIAGNOSIS: A pleural biopsy was performed using a video-assisted thoracoscope. The pathological examination revealed a poorly differentiated squamous cell carcinoma of lung. Further genetic testing identified exon 19 deletion mutation in EGFR with abundance of 0.27%. Meanwhile, immunohistochemical PD-L1 analysis showed a TPS of 90%. INTERVENTIONS: The patient was initially resistant to EGFR-TKIs but exhibited a rapid and marked response to pembrolizumab. OUTCOMES: After 5 cycles of pembrolizumab monotherapy, the patient developed Grade 3 immune-related dermatitis, and ICI therapy was suspended. CONCLUSIONS: ICI monotherapy could be an effective therapy in SQCC patients with low-abundance of EGFR mutations and PD-L1 over-expression. However, close attention should be paid to immune-related adverse events.

Silencing of LncRNA C1RL-AS1 Suppresses the Malignant Phenotype in Gastric Cancer Cells via the AKT/ß-Catenin/c-Myc Pathway.

Purpose: Numerous studies have shown that lncRNAs play vital roles in the development and progression of cancer. However, investigations of lncRNAs in gastric cancer are limited and need to be further pursued. Materials and Methods: According to RNA-seq results of gastric cancer (GC) tissues, we identified a novel lncRNA, C1RL-AS1. qRT-PCR was used to detect the expression level of C1RL-AS1 in paired GC and normal tissues. Nuclear/cytoplasmic fractionation was applied to evaluate the distribution of C1RL-AS1 in GC cells. For functional evaluation, CCK-8, colony formation, transwell, and apoptosis assays were used to determine the oncogenic role of C1RL-AS1. Results: C1RL-AS1 was upregulated in GC tissues, and high expression levels of C1RL-AS1 were associated with poor prognosis. Further in vitro functional assays revealed that silencing C1RL-AS1 attenuated the proliferation rate and migration ability and enhanced the apoptotic rate and the senescence of GC cells. The subsequent underlying mechanistic investigation revealed that Wnt/ß-catenin was involved in C1RL-AS1-mediated signaling. Rescue experiments suggested that C1RL-AS1 probably promoted the malignant phenotype via the AKT/ß-catenin pathway by downregulating c-Myc. Conclusions: C1RL-AS1 probably exerts its biological function by mediating the AKT/ß-catenin/c-Myc pathway, indicating a novel therapeutic target in GC.

Dual drive coexistence of ALK rearrangement and KRAS mutation advanced lung adenocarcinoma and response to crizotinib.

Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene has been considered as a novel oncogenic fusion in a subset of non-small cell lung cancer (NSCLC), mostly in non-smokers with adenocarcinoma. EML4-ALK translocations are commonly reported to be mutually exclusive with epidermal growth factor receptor (EGFR) or KRAS mutations. Herein, we reported a rare case of 47-year-old female was diagnosed with lung adenocarcinoma and treated with three cycles of chemotherapy. A biopsy acquired after disease progression revealed concurrent KRAS mutation and ALK translocation by an next-generation sequencing (NGS) assay. The patient had a favorable tumor response to crizotinib, a tyrosine kinase inhibitor (TKI). A further understanding of the molecular biology with multiple oncogenic drivers will promote the optimal treatment for NSCLC.

Concurrent ROS1 gene rearrangement and KRAS mutation in lung adenocarcinoma: A case report and literature review.

Lung adenocarcinomas with gene rearrangement in the receptor tyrosine kinase ROS1 have emerged as a rare molecular subtype. Although these lung adenocarcinomas respond to ROS1tyrosine kinase inhibitors, many patients ultimately acquire resistance. ROS1gene rearrangement is generally mutually exclusive with other driver genomic alterations, such as those in EGFR, KRAS, or ALK, thus multiple genomic alterations are extremely rare. Herein, we report a case of a 42-year-old man diagnosed with lung adenocarcinoma positive for a SDC4-ROS1 fusion, who was treated with crizotinib followed by three cycles of chemotherapy. A biopsy acquired after disease progression revealed the original SDC4-ROS1 fusion along with a KRAS point mutation (p.G12D).We reviewed the related literature to determine the frequency of gene mutations in non-small cell lung cancer patients. A better understanding of the molecular biology of non-small cell lung cancer with multiple driver genomic aberrations will assist in determining optimal treatment.

Dual drive coexistence of EML4-ALK and TPM3-ROS1 fusion in advanced lung adenocarcinoma.

We report a case of concomitant EML4-ALK and TPM3-ROS1 fusion in non-small cell lung cancer (NSCLC) in a 47-year-old Chinese man and review the clinical characteristics of this type double of fusion. The patient presented with a local tumor of the left upper lobe and underwent thoracoscopy. Postoperative surgical pathologic staging revealed T1a N0 M0 stage IA. Histological examination of the tumor showed lung adenocarcinoma. Ventana ALK (D5F3) assay of the left lung tissue was ALK negative; however, immunohistochemical assay was positive for ROS1 protein. Using next generation sequencing, we found that the tumor had concomitant EML4-ALK and TPM3-ROS1 fusion. No recurrence was observed during seven months of follow-up. Precise diagnostic techniques allow the detection of concomitant ROS1 fusion and other driver genes, including ALK or EGFR; therefore oncologists should consider this rare double mutation in NSCLC patients. Further exploration of treatment models is required to provide additional therapeutic options.

Imaging findings of gastric plexiform fibromyxoma with a cystic change: A case report and review of literature.

RATIONALE: Plexiform fibromyxoma (PF) is an extremely rare mesenchymal tumor of the stomach, and its radiological findings have not been well described. Here, we analyzed the imaging features of a case of PF. To our knowledge, this is a rare reported case with a remarkable cystic change in the imaging literature. PATIENT CONCERNS: A previously healthy 50-year-old woman presented with a 1-day history of abdominal pain. Then, she underwent computed tomography (CT) and magnetic resonance imaging (MRI). A cystic-solid well-circumscribed extraluminal mass was located in the posterior wall of the gastric upper body. The solid portion appeared as heterogeneous attenuation/intensity with progressive enhancement while the cystic region had no enhancement. DIAGNOSES: The potential for malignancy could not be excluded. INTERVENTIONS: Laparoscopic partial gastric resection was performed. OUTCOMES: Based on pathological findings, a diagnosis of PF was made. The patient was alive without any recurrence or metastasis of the tumor after 2 years of follow-up. LESSONS: As far as we know, a gastric PF with a remarkable cystic change has never been reported. Additionally, the tumor exhibited a progressive enhancement pattern which is a characteristic radiographic feature in our case. Our report may help increase the awareness of this rare but important new disease entity.

Impact of Abdominal Shape on Short-Term Surgical Outcome of Laparoscopy-Assisted Distal Gastrectomy for Gastric Cancer.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has been widely accepted for the treatment for gastric cancer. The aim of the present study was to explore the impact of abdominal shape parameters on gastric antrum cancer patients' short-term surgical outcomes of LADG with D2 lymph node dissection in both genders, including the number of lymph nodes retrieved and surgical safety index. METHODS: This was a retrospective analysis of 177 gastric antrum cancer patients, who underwent LADG between April 2009 and January 2016. The abdominal shape parameters, including abdominal anterior-posterior diameter (APD), transverse diameter (TD), xiphoid process of the sternum-navel distance (XND), and thickness of subcutaneous fat (SCF) at the umbilicus level, were calculated by preoperative abdominal computed tomography (CT) scans. The effects of abdominal shape parameters on the short-term surgical outcomes of LADG were analyzed. RESULTS: In male patients undergoing LADG and D2 lymph node dissection, the number of retrieved lymph nodes was significantly lower in patients with APD ≥17.3 cm (P = 0.005), TD ≥27.4 cm (P = 0.029), SCF ≥1.2 cm (P = 0.014), and BMI ≥22.2 (P = 0.008), whereas in female patients, these were statistically insignificant (P > 0.05). APD, TD, SCF, and BMI were negatively correlated with the number of retrieved lymph nodes in male patients. There was no significant difference in the number of lymph nodes retrieved between high-XND group and low-XND group in either gender. Operation time was significantly shorter in male patients with XND < 17.0 cm (P = 0.044) and in female patients with SCF < 2.15 cm (P = 0.013). Intraoperative blood loss and postoperative complication rate were not significantly different between high- and low-APD groups, high- and low-TD groups, high- and low-XND groups, and high- and low-SCF groups in either gender. Compared with male patients, SCF and TD were significantly higher in female patients. In addition, a higher incidence rate of hypertension was observed in patients of both genders with large APD and SCF, although statistically significant only in male patients. CONCLUSIONS: LADG with D2 lymph node dissection can effectively achieve the lymph node dissection requirement of radical distal gastrectomy for patients with various abdominal shapes. It is worth noting that APD, TD, and SCF can impact on lymph node dissection of LADG in male patients. Nevertheless, in female patients, abdominal shape do not impact on lymph node dissection of LADG. Moreover, LADG with D2 lymph node dissection is proved to be safe for various abdominal shape in both genders, even for abdominal obese patients.

Infant pleuropulmonary blastoma: report of a rare case and review of literature.

In infants, pleuropulmonary blastoma is a rare but aggressive tumor. The typical histopathological presentation includes the aggregation of malignant primitive small cells, usually observed in sheets. So as to provide proper and timely treatment, the differential diagnosis includes pulmonary blastoma, sarcomatoid mesothelioma, fetal rhabdomyoma, synovial sarcoma, and primitive neuroectodermal tumor. Herein, we will present one male pediatric patient with pleuropulmonary blastoma. The patient was a 4-month-old male infant, who had a prolonged cough and dyspnea for 4 months that was complicated by cyanosis for 3 days. A physical examination revealed a solid mass in the right lung that was sized 9.0 × 6.0 × 4.0 cm and had a grayish-white cross section. The boundary between the mass and lung tissue was clear; the mass already occupied a great portion of the lung. A microscopic examination suggested that the tumor was composed of round or orbicular-ovate primitive fetal cells. The cells were medium sized, having little cytoplasm, but had a clearly visualized nucleolus and active karyokinesis. The tumor mass was biphasic, namely, fasciculated sarcoma (composed of spindle-shaped cells and short spindle-shaped cells) and malignant fibrous histiocytoma containing well-differentiated cartilage islands or cartilaginous nodes. Immunohistochemistry was performed for further detection: vimentin (+), S-100 protein (+), CK (AE1/AE3), EMA and TTF-1 in residual epithelial components (+), NSE (focal +), SMA (mesenchymal cells, focal +), CD99 (weak +), Bcl-2 (weak +), desmin (-), myoglobin (-), calretinin (-), calponin (-), FLI (-), MyoD-1 (-), and CD34 (-). Pleuropulmonary blastoma is extremely rare but highly aggressive neoplasm in children. Its typical histopathological presentation is the aggregation of primitive malignant small cells. Combining imaging and histopathological examinations and clinical data should help in determining the diagnosis of pleural pulmonary blastoma.

Cytotoxic prenylated bibenzyls and flavonoids from Macaranga kurzii.

One unique prenylated bibenzyl, kurzphenol A (1), two new prenylated flavonoids, kurzphenols B and C (2 and 3), as well as fourteen known compounds (4-17) were isolated from the twigs of Macaranga kurzii. Compound 1 was the first example of prenylated bibenzyl which possesses a benzofuran ring. All the known compounds were isolated from M. kurzii for the first time. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 1-17 were tested for their cytotoxicity against A-549 and Hep G2 cancer cell lines and showed IC50 values in the range of 9.76-30.14 µg/mL.

Imaging findings of primary gastric plasmacytoma: a case report.

Primary gastric plasmacytoma (GP) is a rare extramedullary plasmacytoma with clinical and imaging features that are common among other gastric tumors, such as gastric adenocarcinomas, gastric stromal tumors, and lymphomas. Here, we present a histologically confirmed case of primary GP examined with biphasic computed tomography (CT), magnetic resonance imaging (MRI), and endosonography. A well-circumscribed extraluminal mass appearing as homogeneous attenuation/intensity with gradual enhancement was identified on biphasic enhancement CT and MRI. This mass was hyperintense on diffusion-weighted imaging and hypointense on the apparent diffusion coefficient map, implying that water diffusion in the mass was restricted. In addition, endosonography indicated a low echogenic mass in the gastric wall. These imaging findings increase the available knowledge about imaging of this disease and provide valuable information for differentiating primary GP from common gastric tumors.

Chemical constituents from Euphorbia stracheyi and their biological activities.

Three new diterpenoids, stracheyioids A-C (1-3), as well as 36 known compounds (4-39) were isolated from the whole plants of Euphorbia stracheyi. Compound 1 was a rare 13-deoxy tigliane diterpenoid and compound 2 was an ingenol diterpenoid characterized by an unique 2Z,4Z-decadienoyl acidic moieties. All the known compounds were isolated from E. stracheyi for the first time. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 1-39 were tested for their cytotoxicity against five cancer cell lines (A-549, MCF-7, Hep G2, Hela and P388) and showed IC50 values in the range 6.64-42.86 µM. The antiangiogenic activities of the isolated compounds were also evaluated using a zebrafish model.

Spatial-temporal variations of Schistosoma japonicum distribution after an integrated national control strategy: a cohort in a marshland area of China.

BACKGROUND: Schistosomiasis transmission is typically focal. Understanding spatial variations of Schistosoma infections and their associated factors is important to help to invent site-specific intervention strategies. METHODS: A five-year longitudinal study was carried out prospectively in 12 natural villages, Guichi district of Anhui province. A GIS-based spatial analysis was conducted to identify geographic distribution patterns of schistosomiasis infections at the household scale. RESULTS: The results of the spatial autocorrelation analysis for 2005 showed that there were significant spatial clusters of human infections at the household level, and these results were in agreement with that of the spatial scan statistic. As prevalence of infections in humans decreased over the course of control, the spatial distribution of these infections became less heterogeneous. CONCLUSIONS: The findings imply that it may be necessary to re-assess risk factors of S. japonicum transmission over the course of control and to adjust accordingly control measures in the communities.

[Chemical constituents of Euphorbia sikkimensis].

Sixteen compounds were isolated from the aerial parts of Euphorbia sikkimensis by means of various chromatographic techniques such as silica gel, Sephades LH-20 and RP-18, and their structures were elucidated as naringenin (1), kaempferol (2), quercetin (3), kaempferol-3-O-alpha-L-arabinopyranoside (4), quercetin-3-O-alpha-L-arabinopyranoside (5), quercetin-3-O-(2"-galloyl)-alpha-L-arabinopyranoside (6), 5alpha, 8alpha-epidioxy-(22E, 24R)-ergosta-6,22-dien-3beta-ol (7), stigmast-5-ene-7-one-3beta-ol (8), 3beta-hydroxy4a, 14alpha-dimethyl-5alpha-ergosta-8, 24(28)-dien-7-one(9), beta-sitosterol (10) , 10-cucurbitadienol( 1) , scopoletin(12) , ethyl gallate(13), p-hydroxybenzaldehyde (14), 3 betahydroxybenzeneethanol( 15) ,and 2,4-dihydroxy-6-methoxy-acetophenone (16) on the basis of spectroscopic data analysis. All the compounds are isolated from this plant for the first time, and compounds 1, 4-8, 15 are obtained from Euphorbia species for the first time.

An integrated strategy for transmission control of Schistosoma japonicum in a marshland area of China: findings from a five-year longitudinal survey and mathematical modeling.

In 2004 an aggressive plan was instituted aiming to achieve nationwide transmission control of schistosomiasis by 2015. Here, we report a longitudinal study on the control of schistosomiasis in Anhui province, China. Using a mathematical model, we compared the effects of different control strategies implemented in the study area. During the 5-year study period, a 60.8% reduction in human prevalence was observed from 2005 (7.95%) to 2009 (3.1%), and snail infection decreased from 0.063% in 2005 to zero in 2009. Results of the model agree well with the first 3-year field observations and suggest continuous decrease in human infections in the last 2 years, whereas the last 2-year field observations indicated that human infections appeared to be stable even with continuous control. Our findings showed that the integrated control strategy was effective, and we speculated that other factors besides bovines might contribute to the local transmission of the disease.

Effect of habitat fragmentation on the schistosome-transmitting snail Oncomelania hupensis in a mountainous area of China.

The effect of habitat fragmentation on schistosome-transmitting snails was assessed in an intervention village and a control village in Sichuan Province, China. Snail habitats were fragmented by environmental management. After 2 years, the proportions of quadrats with snails in the fragmented habitats decreased from 9.35% to 2.41% in one patch (c3) and from 12.20% to 6.57% in another patch (c12), whilst the proportions in habitats without fragmentation did not alter significantly. Mean snail density decreased from 0.246 to 0.063 snails/0.11 m2 in patch c3 and from 0.356 to 0.177 snails/0.11 m2 in patch c12, whilst the mean snail density of other patches did not alter significantly. Most snails from the same patch and/or its remaining patches after fragmentation clustered together in the phylogenetic tree, except for c1, c3 and its remaining patches (c5, c6 and c11). Snail habitats in the study zone exhibited visible fragmentation. Habitat fragmentation could decrease the snail population size and limit migration and dispersal of snails between patches.

A longitudinal study of comparison of the Kato-Katz technique and indirect hemagglutination assay (IHA) for the detection of schistosomiasis japonica in China, 2001-2006.

From 2001 to 2006, about one-third of the residents aged 5-65 years were selected as the subjects in a schistosome-endemic village located in Jiangxi Province, China. Every 1 year, all participants were analyzed by the Kato-Katz parasitologic examination and indirect hemagglutination assay (IHA). Statistical analysis of the results showed the k indices ranged from 0.250 to 0.347 between the two methods. Assuming the Kato-Katz results as the gold standard reference, the specificity of the IHA was from 60% to 77%, the positive predictive value of this method was from 19% to 30%, and its sensitivity and negative predictive value were more than 97%. The IHA method is unsuitable for individual screening in endemic community with relatively high prevalence (e.g. with >10% or more prevalence). A search for a better diagnostic test that can be applied in field situations in China is essential and should be given high priority.

[Spatial distribution pattern of Oncomelania hupensis population in marshland and lake area].

OBJECTIVE: To explore the spatial pattern of the distribution of Oncomelania hupensis population in marshland and lake region. METHODS: Four bottomlands were selected randomly for the investigation along the Qiupu River in Guichi District, Anhui Province. The quadrats were placed randomly for snail survey, and the mean crowding, mean density, aggregation indices (diffusion coefficient (C), morisita index (Idelta), index of patchiness (m*/m) ), Taylor's power law and Iwao's m*-m regression index were analyzed. RESULTS: For 4 bottomlands in different time, the diffusion coefficients, Morisita indices, and m*/m indices were all more than one. There was a close linear relationship between the logarithm of the snail density and its variance (P < 0.01), and the correlation coefficient was 0.972. In Taylor's power law, the lg a was 0.602 and b was 1.427. There was a close linear relationship between the mean crowding (m*) and the snail density (m) (P < 0.01), and the correlation coefficient, alpha and beta was 0.984, 2.367 and 1.617 respectively. CONCLUSION: The spatial pattern of Oncomelania hupensis population shows an aggregation distribution in marshland and lake region, and the basic components of snail distribution are in colonies.

[Sequencing on products of Oncomelania hupensis through simple sequence repeat anchored polymerase chain reaction amplification].

OBJECTIVE: To analyze the sequence of microsatellite and the flanking sequence from four populations of Oncomelania hupensis. METHODS: We cloned 159 SSR-PCR amplification products of a commonly used primer, (CA)(8RY), using O. hupensis genomic DNA as template, and sequenced 82 products. RESULTS: The sequences obtained were novel O. hupensis genomic sequences but not repeat simple sequence. It was observed that 36 out of 82 clones contained microsatellites between priming sites. The flanking sequences of certain microsatellite were invariant. Both (GA/CT)(n) and (TTAGGG/CCCTAA)(n) were found in four populations of O. hupensis. However, (CAA)(n) were found only in O. hupensis from Fuqing, Fujian province and (TCTCTG)(n) were found only in O. hupensis from Guichi, Anhui province and (GAA/TTC)(n), (CAA/TTG)(n), (CAT)(n) were found only in O. hupensis from Puge, Sichuan province. CONCLUSION: The results obtained by SSR-PCR should not be interpreted as the amplification of microsatellite loci, and analytical rules similar to those for Random Amplified Polymorphic DNA should be used. SSR-PCR could not make the most of the priority of microsatellite. It seems better to amplify the microsatellites with the primers designed on the basis of the flanking sequence.

[Correlates of and willingness to participate in HIV voluntary counseling and testing among migrants in a city of Shanxi province].

OBJECTIVE: To determine the correlates of and willingness to participate(WTP) in HIV voluntary counseling and testing (VCT) among migrants in Shanxi province. METHODS: Through quota sampling, a total of 1280 migrants were recruited from 6 different venues where migrants were most likely employed to administer a face-to-face anonymous interview. RESULTS: Knowledge of VCT among migrants was low. Only 56.6% of migrants had heard of HIV voluntary counseling and testing. 64.5% reported willingness to accept VCT after participants were informed that HIV counseling and testing was offered free of charge Centers for Disease Prevention and Control (48.7%), hospital (27.0%) and home (18.5%) were most preferred places for VCT service. Logistic regression analysis indicated that the willingness was associated with having a history of HIV test, having better knowledge of HIV, no discrimination against people with HIV, and high HIV/AIDS perception. CONCLUSION: Community-based health education programs for improving HIV/AIDS knowledge, promoting acceptance of VCT and eliminating discrimination to HIV-infected persons were called for.

Field comparison of immunodiagnostic and parasitological techniques for the detection of Schistosomiasis japonica in the People's Republic of China.

A total of 1,811 individuals from two villages located in the areas of China endemic for Schistosoma japonicum were analyzed by the Kato-Katz parasitologic examination, indirect hemagglutination assay (IHA), and enzyme-linked immunosorbent assay (ELISA). Statistical analysis of the results showed the kappa indices ranged from 0.106 to 0.234 between IHA and the stool examination and ranged from 0.037 to 0.134 between ELISA and the fecal examination. The sensitivity value of the IHA was 83.7% in Village A and 92.3% in Village B; the specificity value of the IHA was 55.8% in Village A and 67.3% in Village B. The sensitivity value of the ELISA was 88.4% in Village A and 96.2% in Village B; the specificity value of the ELISA was 38.4% in both Village A and Village B. A search for a good diagnostic test that can be applied in field situations in China should be given high priority.