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Aim: Report the final analysis from ASTRIS, the largest real-world study of second-/later-line osimertinib in advanced/metastatic EGFR T790M non-small-cell lung cancer (NSCLC). Methods: Patients with advanced/metastatic EGFR T790M NSCLC and prior EGFR-TKI treatment, received once-daily osimertinib 80 mg. Primary end point: overall survival (OS); secondary end points: progression-free survival (PFS), time-to-treatment discontinuation (TTD) and response rate. Safety was also recorded. Results: In 3014 patients, median OS: 22.8 months (21.6–23.8), median PFS: 11.1 months (11.0–12.0), median TTD: 13.5 months (12.6–13.9), and response rate: 57.3% (55.5–59.2). All end points reported with 95% CIs. Numerically longer median OS was observed in patients with baseline WHO performance status <2 versus 2 (24.0 vs 11.1 months) and those without versus with brain/leptomeningeal metastases (25.4 vs 18.0 months). No new safety signals were identified. Conclusion: Second-/later-line osimertinib demonstrated real-world clinical benefit and safety in advanced/metastatic EGFR T790M NSCLC. Clinical Trial Registration:NCT02474355 (ClinicalTrials.gov) Osimertinib is a drug that blocks the activity of a protein called EGFR on cancer cells, reducing their growth and spread. ASTRIS is the largest real-world study that evaluated the outcomes with osimertinib treatment for patients with advanced non-small-cell lung cancer (NSCLC), and the EGFR T790M mutation, who had received previous treatment for their cancer. There were 3014 patients included in this study. The main aim of this study was to measure the time at which half of the patients were still alive after starting osimertinib treatment, this was 22.8 months. The study also measured the time at which half of the patients had experienced worsening (progression) of their cancer (11.1 months) and the time when half of the patients had stopped receiving osimertinib treatment (13.5 months). None of the patients experienced any unexpected side effects of the treatment. These data are consistent with those observed in comparable clinical trials with osimertinib, supporting the use of osimertinib treatment for patients with advanced NSCLC and the EGFR T790M mutation after their initial cancer treatment has stopped working. [ABSTRACT FROM AUTHOR]

Background: Recent clinical trials of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in human lung adenocarcinoma (LUAD) have not achieved satisfactory results. The disappointing results of single-drug treatments have prompted studies about synergistic therapies of CDK4/6i with other drugs. We aimed to test the anti-tumor effect of ribociclib (a CDK4/6i) combined with pemetrexed on LUAD and the potential mechanisms. Methods: Cell lines were exposed to ribociclib and pemetrexed at different doses. Antitumor effects were measured using growth inhibition. Cell cycle distribution and apoptosis were evaluated using flow cytometry. Cell migration and invasion were measured using wound healing and transwell invasion assays, respectively. The expression levels of proteins were analyzed using western blotting. Mice xenograft models were used for validation in vivo. Results: Synergism was associated with a combination of cell cycle effects from both agents. Cell cycle analysis revealed that pemetrexed blocked cells in the S phase, whereas ribociclib arrested cells in the G1 phase. Concomitant treatment with pemetrexed and ribociclib resulted in a significantly stronger antitumor ability than treatment alone. We also found that ribociclib strongly enhanced the pro-apoptotic activity of pemetrexed via the caspase/bcl-2 signaling pathway. In addition, we report for the first time that combination treatment with ribociclib and pemetrexed significantly inhibits the migration and invasion of LUAD cells. Conclusions: Combining ribociclib and pemetrexed showed a powerful ability to inhibit cancer proliferation, invasion, and metastasis, and it holds potential as a novel effective combinative therapy for patients with LUAD. [ABSTRACT FROM AUTHOR]

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5–9.8), and the median OS was 26.2 months (95% CI: 24.2–28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS , and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) localize in mammalian ovary, including granulosa cells, cumulus cells, and theca cells. Previous studies demonstrated that TLRs may be important for the cumulus-oocyte complex expansion and fertilization. There is no evidence to indicate that the deletion of TLRs will induce infertility; however, the abnormal expression of TLRs may decrease oocyte quality and fertility rate. In the present study, we investigated the effects of polycystic ovary syndrome (PCOS) on the expression of TLRs in cumulus cells by using western-blot and quantitative real-time PCR (qRT-PCR) analyses. We found that the expression of TLR4 and 9 in cumulus cells was influenced significantly by PCOS. We also observed that overweight/obesity changed the expression of TLR2 and 5 in cumulus cells of PCOS subjects. In addition, we found that the rate of available embryos of women with PCOS was slightly lower. These results indicate that the abnormal expression of TLRs in cumulus may be a reason for the lower embryo quality of women with PCOS. Abbreviations:ART: assisted reproductive technology BMI: body mass index COC: cumulus-cell-oocyte complex PCOS: polycystic ovary syndrome qRT-PCR: quantitative real-time PCR TLRs: Toll-like receptors [ABSTRACT FROM AUTHOR]

We compared clinical outcomes amongst frozen-thawed cleavage-stage embryo, double and single blastocyst transfers in patients requiring whole embryo freezing. Data of infertile patients undergoing in-vitro fertilization and embryo transfer (IVF-ET) in our Reproductive Medicine Center from January 2010 to December 2012 were retrospectively analyzed. According to patients' wishes, patients were divided into cleavage-stage embryo transfer groups (group A, n = 456), double blastocyst transfer group (group B, n = 106), and single blastocyst transfer group (group C, n = 402). We found that the number of frozen embryos was significantly less in groups B and C than in group A (all p < 0.05), but the implantation rate was significantly higher in groups B and C as compared to group A (all p < 0.05). The clinical pregnancy rate and pregnancy rate per included cycle were significantly higher in group B than in groups A and C (all p < 0.05). The multiple pregnancy rate was significantly lower in group C than in groups A and B (all p < 0.05). The rate of early abortion was significantly lower in group C as compared to group A (p < 0.05). The data support the view that it may be the best clinical strategy for patients who require whole embryo freezing and have four or more Day 3 embryos available, to incubate Day 3 embryos into blastocysts, which are then vitrified for elective single blastocyst transfer. [ABSTRACT FROM AUTHOR]

Background: Recently, miR-10b is identified as a miRNA highly expressed in many human cancers, promoting cell migration and invasion. However, the specific function of miR-10b in hepatocellular carcinoma (HCC) is unclear at this point.Methods: The miR-10b expression levels in 60 paired different TNM Stage HCC tumor tissues compared with adjacent non-tumor (ANT) tissues, normal tissue control (8 benign tumor and 7 normal liver tissues), 3 normal liver and 7 HCC cell lines were measured by real-time quantitative RT-PCR and to evaluate their association with HCC clinicopathologic features. Invasion assay, MTT proliferation assay and wound-healing assay were performed to test the invasion and proliferation of HCC cell after transfection. The effect of miR-10b on HCC in vivo was validated by murine xenograft model.Results: We found that miR-10b expression was increased in human HCC tissues and cell lines compared with normal control, respectively. The expression of miR-10b was correlated with HCC metastatic ability. Overexpression of miR-10b in MHCC-97L cells increased cell motility and invasiveness, whereas inhibition of miR-10b in MHCC-97H cells reduced cell motility and invasiveness in vitro and in vivo. We also showed that HOXD10 was negatively regulated by miR-10b at the posttranscriptional level, via a specific target site within the 3'UTR by luciferase reporter assay. Furthermore, we found that miR-10b induced HCC cell invasion and migration by modulating the HOXD10 target gene RhoC, uPAR, MMP-2 and MMP-9 expression.Conclusions: Our results suggested that miR-10b was overexpressed in HCC and promoted HCC cell migration and invasion through the HOXD10/ RhoC/ uPAR/ MMPs pathway which may provide a novel bio-target for HCC therapy. [ABSTRACT FROM AUTHOR]

Ligamentum flavum (LF) hypertrophy (LFH) has been recognised as one of the key contributors to lumbar spinal stenosis. Currently, no effective methods are available to ameliorate this hypertrophy. In this study, human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hUCMSC-EVs) were introduced for the first time as promising vehicles for drug delivery to treat LFH. The downregulation of miR-146a-5p and miR-221-3p expressions in human LF tissues negatively correlated with increased LF thickness. The hUCMSC-EVs enriched with these two miRNAs significantly suppressed LFH in vivo and notably ameliorated the progression of transforming growth factor β1(TGF-β1)-induced fibrosis in vitro after delivering these two miRNAs to mouse LF cells. The results further demonstrated that miR-146a-5p and miR-221-3p directly bonded to the 3'-UTR regions of SMAD4 mRNA, thereby inhibiting the TGF-β/SMAD4 signalling pathway. Therefore, this translational study determined the effectiveness of a hUCMSC-EVs-based approach for the treatment of LFH and revealed the critical target of miR-146a-5p and miR-221-3p. Our findings provide new insights into promising therapeutics using a hUCMSC-EVs-based delivery system for patients with lumbar spinal stenosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors.)

Gastric cancer (GC) is the second most common cancer in China. The ToGA study showed that trastuzumab in combination with fluoropyrimidine plus cisplatin prolonged overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced GC (AGC). However, some patients may not be able to receive this regimen. We conducted a clinical study to evaluate the efficacy and safety of trastuzumab in combination with docetaxel+capecitabine (DX) in patients with HER2-positive AGC. This phase II, multi-center, open-label, single arm study enrolled patients with HER2-positive AGC who had not received prior treatment for metastatic disease. Patients were treated with a regimen of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, day 1), capecitabine (1000 mg/m 2 twice daily, days 1-14) and docetaxel (60 mg/m 2 , day 1 for 6 cycles) every 3 weeks. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), OS and safety profiles. Sixty-seven patients with AGC were enrolled from 14 centers. 64 were included in the full analysis set (FAS). The median PFS was 8.1 months (95% confidence interval [CI]: 5.6-12.8) and the median OS was 20.9 months (95% CI: 15.1-33.0). Response was evaluated in 59 patients. The ORR was 67.8%. The most common adverse events of Grade ≥3 were neutropenia, leukopenia, hand-foot syndrome, febrile neutropenia and anemia. We concluded that combination treatment with trastuzumab and DX was well-tolerated and highly effective in patients with HER2-positive AGC, and may offer an alternative to current treatments., Competing Interests: None., (AJCR Copyright © 2020.)

The notable clinical success of cancer immunotherapy using checkpoint blockade suggests that it is likely to form the foundation of curative therapy for many malignancies. However, checkpoint blockades do not achieve sustained clinical response in most patients and thus amounts of problems needed to be figured out. Regarding these challenges, the 2017 Chinese Lung Cancer Summit expert panel organized a forum on the 14th Chinese Lung Cancer Summit to formally discuss these controversies. Five consensuses finally were reached to guide the application of checkpoint blockades., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Mucinous adenocarcinoma is an unusual histological type of lung cancer, and its clinicopathological feature is distinctive from that of other histopathological types of lung adenocarcinoma. Mucinous adenocarcinoma has a mucus-producing function, which explains its name. The present study reports a rare case of a mucus-producing adenocarcinoma of the lung. A 60-year-old Chinese female patient was diagnosed with mucinous adenocarcinoma of the lung, which manifested as respiratory symptoms, including fever, cough and expectoration. The patient received thoracic exploratory operation and right pneumonectomy, since the above respiratory symptoms seriously affected her daily life, and other inspections could not establish the diagnosis. Histopathology revealed no mutations in epidermal growth factor receptor. The patient received adjuvant chemotherapy using taxol and cisplatin. However, metastases in the left lung were detected 7 months after the operation. Pemetrexed and cisplatin were used as the second-line treatment. The patient survived 3 years after the initial diagnosis. The present study reports a rare mucus-producing adenocarcinoma of the lung, which is of bad prognosis. Therefore, further studies on this type of cancer are urgently required.

Background: The granisetron transdermal delivery system (GTDS) has been demonstrated effectiveness in the control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of GTDS in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in China., Methods: A total of 313 patients were randomized into the GTDS group (one transdermal granisetron patch, 7 days) or the oral granisetron group (granisetron oral 2 mg/day, ≥2 days). The primary endpoint was the percentage of patients achieving complete control (CC) from chemotherapy initiation until 24 h after final administration (PEEP). Chi-square test and Fisher's exact test were used for statistical analysis., Results: Two hundred eighty-one patients were included in the per protocol analysis. During PEEP, CC was achieved by 67 (47.52%) patients in the GTDS group and 83 (59.29%) patients in the oral granisetron group. There was no statistical significance between the groups (P=0.0559). However, the difference of the CC percentage mainly occurred on the first day of chemotherapy between the groups. The CC was 70.13% on day 1 in the GTDS group, which was significantly lower than that of 91.03% in the oral granisetron group in the full analysis set. In the following days of chemotherapy, the CC was similar between the groups. In terms of cisplatin-contained regimen and female, there was statistical significance between the groups. Both treatments were well tolerated and safe. The most common adverse event was constipation., Conclusions: GTDS provided effective and well-tolerated control of CINV in Chinese patients, especially to non-cisplatin-contained regimen.

Purpose: The number of cancer cases in China has increased rapidly from 2.1 million in 2000 to 4.3 million in 2015. As a consequence, pain management as an integral part of cancer treatment became an important health care issue. In March 2011, the Good Pain Management (GPM) program was launched to standardize the treatment of cancer pain and improve the quality of life for patients with cancer. With this work, we will describe the GPM program, its implementation experience, and highlight key lessons that can improve pain management for patients with cancer., Methods: We describe procedures for the selection, implementation, and assessment procedures for model cancer wards. We analyzed published results in areas of staff training and patient education, pain management in practice, analgesic drugs administration, and patient follow-up and satisfaction., Results: Pain management training enabled medical staff to accurately assess the level of pain and to provide effective pain relief through timely dispensation of medication. Patients with good knowledge of treatment of pain were able to overcome their aversion to opioid drugs and cooperate with nursing staff on pain assessment to achieve effective drug dose titration. Consumption of strong opioid drugs increased significantly; however, there was no change for weaker opioids. Higher pain remission rates were achieved for patients with moderate-to-severe pain levels. Proper patient follow-up after discharge enabled improved outcomes to be maintained., Conclusion: The GPM program has instituted a consistent and high standard of care for pain management at cancer wards and improved the quality of life for patients with cancer., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Shi-Ying YuNo relationship to discloseJie-Jun WangNo relationship to discloseYu-guang HuangNo relationship to discloseBing HuNo relationship to discloseKun WangNo relationship to disclosePing Ping LiNo relationship to discloseYi-Long WuHonoraria: AstraZeneca, Eli Lilly, Roche, Pierre Fabre, Pfizer, Sanofi Consulting or Advisory Role: AstraZeneca, Roche, Merck, Boehringer Ingelheim Research Funding: Boehringer Ingelheim (Inst), Roche (Inst)He-Long ZhangNo relationship to discloseLi ZhangResearch Funding: Eli Lilly, AstraZeneca, Novartis, Bristol-Myers Squibb, Boehringer IngelheimQing-Yuan ZhangNo relationship to discloseShu-Kui QinNo relationship to disclose

Accumulating evidence suggests that the tumor suppressor gene Krüppel-like factor 6 (KLF6) plays important roles in both development and progression of cancer. However, the role of KLF6 in hepatocellular carcinoma (HCC) remains unclear. Cancer-related molecule basigin-2 plays an important role in HCC progression and metastasis. Sp1, one of Sp/KLFs family members, regulates basigin-2 expression in HCC. The involvement of KLFs in basigin-2 regulation and HCC progression and metastasis has not been investigated. We first measured KLF6 expression levels in 50 pairs of HCC and adjacent normal tissues (ANTs) by immunohistochemistry. Specifically, low KLF6 expression but high Sp1 and basigin-2 expression were found in HCC tissues. By contrast, the ANTs showed high KLF6 expression but low Sp1 and basigin-2 expression. Kaplan-Meier analysis showed that higher expression of KLF6 was associated with better overall survival. The survival rate of KLF6-negative patients was lower than that of KLF6-positive patients (P = 0.015). We also found that KLF6 binds to the basigin-2 and Sp1 promoters and decreases their expression. Thus, we identified a microcircuitry mechanism in which KLF6 can repress basigin-2 expression directly by binding to its promoter or indirectly by inhibiting the expression of the transcription factor Sp1 to block gene expression. Additionally, overexpression of KLF6 suppressed the invasion, metastasis and proliferation of HCC cells in vitro and in vivo by targeting basigin-2. Our study provides new evidence that interaction of KLF6 and Sp1 regulates basigin-2 expression in HCC and that KLF6 represses the invasive and metastatic capacities of HCC through basigin-2., Competing Interests: The authors have declared that no competing interests exist.

Background: Lung cancer bone metastasis causes poor prognosis. Basigin-2, a novel cancer-associated biomarker, is upregulated in lung cancer and has been linked with tumor progression. But little is known about the role of basigin-2 in lung cancer bone metastasis and osteolytic lesion., Methods: Basigin-2 expression was evaluated in biopsy tissue specimens of 20 lung cancer patients with bone metastases via immunohistochemistry. Invasion assay and MTT proliferation assay were performed to test the invasion and proliferation of lung cancer cell after modulated basigin-2 expression. The osteoclastic activity of basigin-2 was detected in tibia cancer model by injected of lung cancer cells. The regulation role of receptor activator of NF-κB ligand (RANKL) on basigin-2 and its downstream molecules were measured by real-time quantitative RT-PCR, gelatin zymography and western blot analysis., Results: We found that basigin-2 was highly expressed in lung cancer bone metastases. Then, we demonstrated that basigin-2 could promote lung cancer cells invasion, metastasis and proliferation through upregulating metalloproteinases-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression. The lung cancer cells overexpressing basigin-2 strongly induced the osteolytic lesions in immunodeficient mice, which were reduced by treatment with basigin-2 blocking antibody. Furthermore, we explored the enhanced basigin-2 molecular mechanism in lung cancer bone metastasis. Our results indicated the RANKL, pivotal for the control of bone resorption, could increase basigin-2 and its downstream molecules MMP-2, MMP-9 and VEGF expression in vitro., Conclusions: Basigin-2 upregulated by RANKL induces MMPs and VEGF, which may increase lung cancer cell metastasis ability and support osteoclastic activity. Thus, our data suggest important roles for basigin-2 in lung cancer-induced osteolytic lesion and implicate this protein potential application as a target for lung cancer bone metastasis therapy.

The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China.

Introduction: Bone metastasis (BM) in patients with primary lung cancer poses a serious health problem. Numerous risk factors have been hypothesised to predict BM in these patients, but research studies are of mutable quality, and may not be of value in clinical evaluation., Methods and Analysis: We will search a number of electronic databases including PubMed, MEDLINE, Web of Science, EMBASE, the Cochrane Library (Cochrane Database of Systematic Reviews) and the Cochrane Central Register of Controlled Trials (CENTRAL). We will carry out a secondary search for articles from references of included articles (from January 1990 to June 2014). Primary and secondary outcomes will be BM and skeletal-related events information. We will summarise the effect estimates of risk factors and use random-effect models to pool the estimates, if the outcomes and characteristics in studies are comparable. The quality of the study will be assessed using the Newcastle-Ottawa Scale and the Cochrane Collaboration tool., Trial Registration Number: CRD42013003744., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Gastrointestinal stromal tumors (GISTs) are rare, and account for 1% of all gastrointestinal neoplasms. GISTs are the most frequent mesenchymal tumors of the gastrointestinal tract. However, the clinical and pathological characteristics of these neoplasms are not adequately understood. The best treatment approach for GISTs remains unclear. In the present study, we report a case of a GIST originating from the stomach. A digestive tract hemorrhage occurred as a complication of sunitinib treatment. This is the first report of a digestive tract hemorrhage due to sunitinib treatment.

Objective: To compare the efficacy and safety of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), and a single subcutaneous injection of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF), a sustained-duration rhG-CSF, in chemotherapy-induced neutropenia., Methods: In the present randomized, open-label, match and cross-over study, enrolled 104 patients with previously untreated non-small cell lung cancer (NSCLC), breast cancer or non-Hodgkin's lymphoma and with normal bone marrow function from 13 centers were randomly divided into 2 matched groups, AB and BA group. Each patient received two cycles of chemotherapy of identical regimen. In the study cycle, the patients received a single subcutaneous injection of PEG-rhG-CSF 100 microg/kg on day 3; and in control cycle, daily subcutaneous infection of rhG-CSF 5 microg x kg(-1) x d(-1) began on day 3 and continued for 14 days or until the absolute neutrophil count (ANC) became > or = 5.0 x 10(9)/L twice after it decreased to the nadir. Efficacy and safety parameters were monitored., Results: The incidence rates of ANC < 1.5 x 10(9)/L in the 103 evaluable study cycles and 100 evaluable control cycles were 30.00% and 20.00% with the duration of 2.39 days and 2.35 days respectively. The incidence rates of grade 3 neutropenia were 7.77% and 7.00%; and that of grade 4 neutropenia were 5.80% and 4.00% respectively in the trial and control cycles. However, all the difference mentioned above did not reached statistical significance. None of the patients experienced febrile neutropenia. The ANC nadir was (7.55 +/- 5.25) x 10(9)/L and (8.42 +/- 5.57) x 10(9)/L (P = 0.257) respectively after receiving PEG-rhG-CSF and rhG-CSF. Compared with that of rhG-CSF group, the ANC profile of PEG-rhG-CSF group exhibited limited "overshoot" of neutrophils after the nadir. Subgroup analysis according to disease type yielded similar results. The safety profiles of the PEG-rhG-CSF and rhG-CSF groups were similar. Musculoskeletal pain or arthralgia occurred in 16.5% of the study cycles and 26.00% of the control cycles (P = 0.963), mostly mild or moderate. Other adverse effects such as fever, fatigue, dizziness, gastrointestinal effects and injection-site pain, were transient and easily manageable., Conclusion: A single subcutaneous injection of PEG-rhG-CSF 100 microg/kg provides neutrophil support and a safety profile comparable to regimen of daily subcutaneous injection of rhG-CSF 5 microg x kg(-1) x d(-1) in Chinese patients receiving a variety of myelosuppressive chemotherapy regimens.

The skewed X chromosome inactivation (SXCI) was found mainly in adult females. It has been linked to development of ovarian and breast cancers. The present study aimed to describe the relationship between SXCI and development of lung cancer in females. DNA was isolated from blood cells from patients with primary lung cancer (n=148) and reference subjects (n=289). The androgen receptor (AR) gene exon 1 was amplified, with its products from different alleles resolved on denaturing polyacrylamide gels and visualized by silver staining. The corrected ratio (CR) between products from AR alleles after and before HpaII pretreatment was calculated. Occurrence of SXCI was detected in both the patients and reference subjects at similar frequency. However, the phenomenon was more frequent in the patients below 40 years compared to the corresponding reference group, either taking CR >/=3 (25 and 5.8%, respectively; P=0.048) or CR >/=10 as the criterion of SXCI (16.7 and 0.8%, respectively; P=0.022). A higher frequency of SXCI was also found in the patients below 50 years compared to that for the corresponding reference group when CR >/=10 adopted as the criterion (7.9 and 1.2%, respectively; P=0.046). The cancer patients with SXCI were more than 10 years younger in average age than those without SXCI. SXCI of blood cells is associated with early development of lung cancer in females. The X chromosomal inactivation assay, therefore, may be used to screen for females predisposed to malignancies including lung cancer.

Objective: To observe the relationship between skewed X-chromosomal inactivation (SXCI) and development of lung cancer in females., Methods: DNA was isolated from peripheral blood cells from patients with primary lung cancer (n = 148) and control subjects (n =289). Exon 1 of androgen receptor ( AR) gene was amplified, with its products from different alleles resolved on denaturing polyacrylamide gels and visualized by silver staining. The corrected ratio (CR) between products from different AR alleles before and after Hpa II pretreatment was calculated. All statistical tests were two-sided., Results: With CR> or = 10 adopted as the criterion, SXCI was found more frequently in the younger patients ( C50 years; 7. 9%) than in the controls of the same age group (1. 2% ; P = 0. 046). The SXCI frequency, however, were not significantly different between the old patients ( > 50 years; 4. 5% ) and the controls of the same age group (5. 4% ; P =0. 488). Whether taking CR> or =3 or CR> or =10 as the criteria, the average ages of the patients with SXCI were more than 10 years younger than those without SXCI (P < 0. 05)., Conclusion: SXCI in blood cells is associated with early development of lung cancer in females.