Effect of CDK4/6 Inhibitors on Tumor Immune Microenvironment.

Cancer is an abnormal proliferation of cells that is stimulated by cyclin-dependent kinases (CDKs) and defective cell cycle regulation. The essential agent that drive the cell cycle, CDK4/6, would be activated by proliferative signals. Activated CDK4/6 results in the phosphorylation of the neuroblastoma protein (RB) and the release of the transcription factor E2F, which promotes the cell cycle progression. CDK4/6 inhibitor (CDK4/6i) has been currently a research focus, which inhibits the CDK4/6-RB-E2F axis, thereby reducing the cell cycle transition from G1 to S phase and mediating the cell cycle arrest. This action helps achieve an anti-tumor effect. Recent research has demonstrated that CDK4/6i, in addition to contributing to cell cycle arrest, is also essential for the interaction between the tumor cells and the host immune system, i.e., activating the immune system, strengthening the tumor antigen presentation, and reducing the number of regulatory T cells (Treg). Additionally, CDK4/6i would elevate the level of PD-L1, an immunosuppressive factor, in tumor cells, and CDK4/6i in combination with anti-PD-L1 therapy would more effectively reduce the tumor growth. Our results showed that CDK4/6i caused autophagy and senescence in tumor cells. Herein, the impact of CDK4/6i on the immune microenvironment of malignant tumors was mainly focused, as well as their interaction with immune checkpoint inhibitors in affecting anti-tumor immunity.

Impact of endogenous glucocorticoid on response to immune checkpoint blockade in patients with advanced cancer.

Background: Previous studies indicate that exogenous use of glucocorticoid (GC) affects immune checkpoint inhibitor (ICI) efficacy. However, there is a paucity of clinical data evaluating the direct impact of endogenous GC on the efficacy for cancer patients with immune checkpoint blockade. Methods: We first compared the endogenous circulating GC levels in healthy individuals and patients with cancer. We next retrospectively reviewed patients with advanced cancer with PD-1/PD-L1 inhibitor alone or combination therapy in a single center. The effects of baseline circulating GC levels on objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analyzed. The association of the endogenous GC levels with circulating lymphocytes, cytokines levels, and neutrophil to lymphocyte ratio, and tumor infiltrating immune cells, were systematically analyzed. Results: The endogenous GC levels in advanced cancer patients were higher than those in early-stage cancer patients as well as healthy people. In the advanced cancer cohort with immune checkpoint blockade (n=130), patients with high baseline endogenous GC levels (n=80) had a significantly reduced ORR (10.0% vs 40.0%; p<0.0001) and DCB (35.0% vs 73.5%, p=0.001) compared to those with low endogenous GC levels (n=50). The increased GC levels was significantly associated with reduced PFS (HR 2.023; p=0.0008) and OS (HR 2.809; p=0.0005). Moreover, statistically significant differences regarding PFS, and OS were also detected after propensity score matching. In a multivariable model, the endogenous GC was identified as an independent indicator for predicting PFS (HR 1.779; p=0.012) and OS (HR 2.468; p=0.013). High endogenous GC levels were significantly associated with reduced lymphocytes (p=0.019), increased neutrophil to lymphocyte ratio (p=0.0009), and increased interleukin-6 levels (p=0.025). Patients with high levels of endogenous GC had low numbers of tumor infiltrating CD3+ (p=0.001), CD8+ T (p=0.059), and CD4+ T (p=0.002) cells, and the numbers of circulating PD-1+ NK cells (p=0.012), and the ratio of CD8+PD-1+ to CD4+PD-1+ (p=0.031) were higher in patients with high levels of endogenous GC compared to low levels of endogenous GC. Conclusion: Baseline endogenous GC increase executes a comprehensive negative effect on immunosurveillance and response to immunotherapy in real-world cancer patients accompanied with cancer progression.

Myocarditis and myositis/myasthenia gravis overlap syndrome induced by immune checkpoint inhibitor followed by esophageal hiatal hernia: A case report and review of the literature.

Immunotherapy with programmed death 1 (PD-1) inhibitor has shown activity as first- or second-line treatment for various metastatic human malignancies. Immune-related adverse events (irAEs) are now well-described, and most organ sites are potentially influenced, but the prevalence of myocarditis and myositis/myasthenia gravis (MG) overlap syndrome following esophageal hiatal hernia induced by immunotherapy is rarely reported. Here, we describe a 71-year-old woman with a progressed unresectable extrahepatic cholangiocarcinoma and biliary obstruction. She had no prior history of muscle weakness and neuromuscular disease with a normal body mass index. She was treated with sintilimab as a rescue regimen of immunotherapy. After the first cycle of treatment, she experienced a grade 4 myopathy including simultaneous myositis, myalgia, and myocarditis due to multiple injuries in her cardiac, skeletal, and ocular muscles. She had elevated levels of creatine kinase (CK), cardiac troponin I, and myoglobin (MYO), but MG and myositis-specific and myositis-related antibodies were negative. Immunotherapy was discontinued and pulse high-dose methylprednisolone with a slow tapering and intravenous immunoglobulin (IVIG) was initiated. Two weeks later, the patient's clinical presentation improved significantly. A subsequent cardiac magnetic resonance (MR) examination revealed an old myocardial injury that may be a result of immune-related cardiac toxicity. In the third month following the PD-1 inhibitor therapy, she restarted systemic chemotherapy in combination with an anti-angiogenic agent but without immunotherapy. Half a year later, she complained of repeated abdominal distension and radiographic examinations and endoscopy showed a clinically confirmed diagnosis of sliding hiatal hernia of the esophagus and gastroesophageal reflux disease. Due to mild symptoms associated with gastroesophageal reflux, she was suggested close monitoring with acid secretion blockade rather than immediate surgical intervention. The severity for patients with myositis and myocarditis accompanied without MG is similar to those with MG. Considering the use of PD-1 inhibitors is increasing in cancer patients, physicians should therefore pay more attention to immunotherapy-induced myocarditis with myositis/MG overlap syndrome. Since we hypothesize diaphragmatic hiatal hernia as a potential consequence of immunotherapy-induced myositis, reports on hiatal hernias subsequent to immunotherapy-induced myositis are needed.

Research progress on the effect of gut and tumor microbiota on antitumor efficacy and adverse effects of chemotherapy drugs.

Chemotherapy is one of the most effective methods of systemic cancer treatment. Chemotherapy drugs are delivered through the blood circulation system, and they can act at all stages of the cell cycle, and can target DNA, topoisomerase, or tubulin to prevent the growth and proliferation of cancer cells. However, due to the lack of specific targets for chemotherapeutic agents, there are still unavoidable complications of cytotoxic effects. The effect of the microbiome on human health is clear. There is growing evidence of the potential relationship between the microbiome and the efficacy of cancer therapy. Gut microbiota can regulate the metabolism of drugs in several ways. The presence of bacteria in the tumor environment can also affect the response to cancer therapy by altering the chemical structure of chemotherapeutic agents and affecting their activity and local concentration. However, the underlying mechanisms by which the gut and tumor microbiota affect cancer therapeutic response are unclear. This review provides an overview of the effects of gut and tumor microbiota on the efficacy and adverse effects of chemotherapy in cancer patients, thus facilitating personalized treatment strategies for cancer patients.

Immune-related dissociated response as a specific atypical response pattern in solid tumors with immune checkpoint blockade.

Immune checkpoint blockade using immune checkpoint inhibitors, including cytotoxic T-lymphocyte-associated antigen-4 and programmed cell death protein-1/programmed cell death ligand-1 inhibitors, has revolutionized systematic treatment for advanced solid tumors, with unprecedented survival benefit and tolerable toxicity. Nivolumab, pembrolizumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab are currently approved standard treatment options for various human cancer types. The response rate to immune checkpoint inhibitors, however, is unsatisfactory, and unexpectedly, atypical radiological responses, including delayed responses, pseudoprogression, hyperprogression, and dissociated responses (DRs), are observed in a small subgroup of patients. The benefit of immunotherapy for advanced patients who exhibit atypical responses is underestimated according to the conventional response evaluation criteria in solid tumors (RECIST). In particular, DR is considered a mixed radiological or heterogeneous response pattern when responding and nonresponding lesions or new lesions coexist simultaneously. The rate of DR reported in different studies encompass a wide range of 3.3-47.8% based on diverse definition of DR. Although DR is also associated with treatment efficacy and a favorable prognosis, it is different from pseudoprogression, which has concordant progressive lesions and can be regularly captured by immune RECIST. This review article aims to comprehensively determine the frequency, definition, radiological evaluation, probable molecular mechanisms, prognosis, and clinical management of immune-related DR and help clinicians and radiologists objectively and correctly interpret this specific atypical response and better understand and manage cancer patients with immunotherapy and guarantee their best clinical benefit.

Dynamics of Early Serum Tumour Markers and Neutrophil-to-Lymphocyte Ratio Predict Response to PD-1/PD-L1 Inhibitors in Advanced Non-Small-Cell Lung Cancer.

PURPOSE: To evaluate the dynamics of early serum tumour markers (STMs) and the neutrophil-to-lymphocyte ratio (NLR) to predict clinical efficacy and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who received programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors. PATIENTS AND METHODS: We retrospectively reviewed patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors between September 2017 and August 2020. NLR and STMs were routinely measured between immunotherapy initiation and the first radiological evaluation. A combination score based on the leading STM and NLR and their dynamic changes was established. The effects of leading STM change, NLR change, and the combination score on the objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analysed. The accuracy of the combination score was evaluated by receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: Overall, 124 patients were included in this retrospective cohort study. The ORR was 22.8%, DCB was 54.5%, and the median OS and PFS were 21.6 and 14.9 months, respectively. Patients with low combination scores had a significantly improved ORR and DCB compared with those with intermediate or high scores (P = 0.002 for ORR, P < 0.0001 for DCB). In a multivariate model, the combination score was an independent indicator of PFS (P < 0.0001) and OS (P < 0.0001). The AUC demonstrated that the combination score (AUC = 0.706) has greater predictive power than either the posttreatment NLR (AUC = 0.668) or the leading STM change (AUC = 0.648) alone. CONCLUSION: An easy, cost-effective, and novel combination score based on the dynamics of an early STM and the NLR can accurately predict the clinical efficacy of PD-1/PD-L1 inhibitors and prognosis in advanced NSCLC patients.

Excellent Response to Atezolizumab After Clinically Defined Hyperprogression Upon Previous Treatment With Pembrolizumab in Metastatic Triple-Negative Breast Cancer: A Case Report and Review of the Literature.

Immunotherapy with immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors, has revolutionized the systematic treatment of advanced and metastatic solid tumors. However, the response rate to ICIs is unsatisfactory, and unexpected hyperprogressive disease (HPD) is even observed in a small subgroup of patients. Patients with HPD usually have worsening clinical symptoms and poorer survival, and therapeutic strategies are extremely limited. Here, we presented a patient with HPD who had used a PD-L1 inhibitor and was highly responsive to the sequential use of a PD-1 inhibitor. A 67-year-old woman with metastatic triple-negative breast cancer was treated with pembrolizumab plus chemotherapy after progression on previous multiple-line chemotherapy treatments. After 2 cycles of treatments, she rapidly developed HPD, as confirmed by radiological evaluation and worsening symptoms. At that time, pembrolizumab was discontinued, and she switched to the PD-L1 inhibitor atezolizumab plus chemotherapy. This patient partially responded to atezolizumab plus chemotherapy without experiencing severe drug-related adverse effects. This is the first reported case of metastatic breast cancer in a patient with radiologically confirmed HPD after pembrolizumab therapy in which successful rechallenge with atezolizumab relieved clinical symptoms. Further studies with larger sample sizes involving a deeper translational investigation of HPD are needed to confirm the efficacy and mechanism of sequential application of different ICIs for the clinical management of HPD.

Primary Squamous Cell Carcinoma of the Liver is Rare but Hostile: Case Series and Comprehensive Review of the Literature.

Primary squamous cell carcinoma (SCC) of the liver is an uncommon cancer type. Only dozens of such cases have been reported in the literature. We reviewed three cases with primary SCC of the liver in a single center from January 2013 to October 2019. One case was positive for hepatitis B infection and simultaneously diagnosed with sigmoid adenocarcinoma and liver cyst. The second patient presented with hepatolithiasis. The remaining one had no history of prior liver insult, hepatic infection or any pre-existing hepatic cysts. Two cases had a long survival of more than one year through chemotherapy, or radical surgery plus transarterial chemoembolization. We also found 25 patients with primary hepatic SCC in the Surveillance, Epidemiology and End Results (SEER) database from 1997 to 2016. The median age was 67 years (range 33-87 years). The median overall survival and disease-specific survival were 7.7 months (range 0.0-76.0 months) and 2.0 months (range 0.0-20.0 months), respectively. Furthermore, patients receiving surgery had a longer median OS (20.0 versus 6.0 months, P = 0.016) and DSS (48.0 versus 8.0 months, P = 0.03) than those receiving palliative treatment. Only 20% of all cases survived for more than a year. Although primary SCC of the liver has an unfavorable prognosis, radical surgery and systematic treatment might be helpful for clinical management.

Misdiagnosis of primary intimal sarcoma of the pulmonary artery as chronic pulmonary embolism: A case report.

BACKGROUND: Primary intimal sarcoma of the pulmonary artery is a rare malignant tumor originating from the pulmonary artery, which has a low incidence rate and is easily misdiagnosed as pulmonary embolism. There is no standard protocol for the treatment of primary intimal sarcoma of the pulmonary artery. CASE SUMMARY: This study reports a patient with primary intimal sarcoma of the pulmonary artery who was admitted to our hospital in 2017. The clinical characteristics, diagnosis, treatment and outcome of the patient were retrospectively analyzed. The patient was a Chinese Han male aged 44 years. He had three consecutive episodes of syncope, and was thus admitted to a local hospital. Computed tomography pulmonary angiography showed multiple lesions with abnormal densities in the pulmonary trunk, left pulmonary artery, mediastinum and pericardium, which were consistent with recurrence after tumor resection. He underwent surgery, and was pathologically diagnosed with intimal sarcoma of the pulmonary artery. He relapsed 3 mo after surgery, and apatinib was administered. His condition was stable after 4 mo, with tolerable and controllable adverse reactions. He subsequently died 19 mo after surgery. CONCLUSION: Primary intimal sarcoma of the pulmonary artery has no specific clinical or imaging manifestations. The diagnosis of this disease depends on histopathology and immunohistochemistry, and has a poor clinical prognosis. Surgical treatment is currently a favorable option for primary intimal sarcoma of the pulmonary artery, and targeted therapy may provide new insights for the development of effective treatment methods.

Immune-related organizing pneumonitis in non-small cell lung cancer receiving PD-1 inhibitor treatment: A case report and literature review.

Immune checkpoint blockade with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors has been standard care for metastatic nonsmall cell lung cancer (NSCLC) and after progression using first-line platinum-containing chemotherapy. Although several management guidelines exist for immune checkpoint inhibitor-induced toxicities, uncommon, complicated, and life-threatening immune-related adverse events remain challenging for oncologists. In this report, we presented a male patient with NSCLC who received pembrolizumab during disease progression. He developed interstitial pembrolizumab-induced organizing pneumonia (OP). The patient received 9 months of anti-PD-1 pembrolizumab when he presented with dry cough and fatigue. The patient developed a solitary nodular lung lesion mimicking a newly occurred metastatic lesion in the lung without a significant circulating tumor marker increase. Sputum analysis was negative for acid-fast bacilli and fungi. A computed tomography-guided percutaneous lung biopsy was conducted and showed alveolar fibrous thickness and various lymphocyte infiltration. Immunotherapy-related OP was identified, and he subsequently responded well to corticosteroids. This case describes a clinical situation, where PD-1-induced OP is radiologically similar to NSCLC disease progression in the lungs. Oncologists should be aware of uncommon pulmonary PD-1/PD-L1 inhibitor toxicity. Lung biopsy may help to distinguish immune-related pneumonitis, lung infections, and progressive nodular lesions.

MicroRNA-138 Suppresses Osteoblastic Differentiation of Valvular Interstitial Cells in Degenerative Calcific Aortic Valve Disease.

The aim of this study was to explore the function of miR-138 in the pathogenesis of degenerative calcific aortic valve disease (DCAVD).Aortic valve calcification tissue and normal tissue from DCAVD patients were collected to detect the expression of miR-138 by qRT-PCR, and immunohistochemical staining was performed to identify the phenotype of valve interstitial cells. QRT-PCR was performed to analyze the expression of miR-138, Runx2, MSX2, and ALP at day 7 after osteogenic differentiation. Alkaline phosphatase activity assay was performed at day 14 after osteogenic differentiation. Alizarin red staining was used to analyze the calcium nodule formation. TargetScan was used to predict potential targets of miR-138. QRT-PCR and Western blotting were performed to analyze the expression of FOXC1 in valve interstitial cells (VICs). The aortic valve calcification was evaluated by quantitative analysis of the velocity in the aortic annulus and transvalvular pressure gradients.In this study, we demonstrated the role of miR-138 in VIC osteogenesis. QRT-PCR results revealed miR-138 was significantly down-regulated in calcified aortic valves compared with non-calcified valves. MiR-138 overexpression inhibited VIC osteogenic differentiation in vitro, while down-regulation of miR-138 enhanced the process. Target prediction analysis and dual-luciferase reporter assay confirmed FOXC1 was a direct target of miR-138. Further research found FOXC1 overexpression promoted VIC osteogenic differentiation. In addition, animal experiments validated indirectly miR-138 could suppress aortic valve calcification.Our findings suggest miR-138 could function as a new inhibitor of VIC osteogenic differentiation, which may act by targeting FOXC1.

Endostatin reverses immunosuppression of the tumor microenvironment in lung carcinoma.

Endostatin has previously been demonstrated to efficiently inhibit the angiogenesis and growth of endothelial cells. However, the role of endostatin in the tumor microenvironment remains to be elucidated. To investigate the antitumor effect of endostatin in lung cancer, the present study was designed to explore the alterations of microvessel density in Lewis lung cancer models and the expression of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-17, interferon (IFN)-γ and hypoxia inducible factor (HIF)-1α, following endostatin therapy. It was demonstrated that the growth and angiogenesis of tumors were markedly suppressed by treatment with endostatin, compared with control group. The microvessel density in mice treated with endostatin was significantly inhibited in a dose-dependent manner. The expression levels of VEGF, IL-6 and IL-17 in tumors were decreased, however IFN-γ and HIF-1α expression levels were increased, following treatment with endostatin. In addition, the proportion of myeloid derived suppressor cells and tumor associated macrophages (TAMs; M2 type) were significantly decreased, whereas those of mature dendritic cells and TAMs (M1 type) were increased, and cluster of differentiation (CD)8+ T cells were recruited to infiltrate the tumors following treatment with endostatin. In addition, the expression levels of IL-6, IL-10, tumor growth factor-ß and IL-17 in tumor tissue were potently decreased with endostatin therapy. These results indicated that endostatin efficiently inhibited tumor angiogenesis and reversed the immunosuppressive microenvironment associated with the presence of tumors.

Association between obesity and trastuzumab-related cardiac toxicity in elderly patients with breast cancer.

PURPOSE: Trastuzumab can improve the prognosis for patients with breast cancer, but its related cardiac toxicity is concerning. This study aimed to identify the risk factors associated with trastuzumab-related cardiac toxicity in elderly patients with HER2-positive breast cancer. PATIENTS AND METHODS: A total of 133 elderly (≥ 65 years) patients who were diagnosed with breast cancer between June 1, 2007, and January 31, 2016, and received trastuzumab treatment were retrospectively reviewed. Cardiac events were defined as: (1) LVEF reduction of >10% from baseline echocardiography, (2) reduction of LVEF to <50%, and (3) signs and symptoms of heart failure as defined by the Common Terminology Criteria for Adverse Events (CTCAE) accompanied by a decrease in the LVEF. Univariate and multivariate regression analyses were used to determine the contribution of different clinical variables to trastuzumab-related cardiac events. RESULTS: The median age of the cohort was 71.0 years (range, 65-81 years). The median follow-up period for measurement of left ventricular ejection fraction was 11.0 months (range, 2-71 months). Fifteen patients (11.2%) experienced cardiac events during the follow-up. Multivariate regression analysis revealed that obesity (odd ratio[OR], 4.706; 95% CI, 1.984-10.147; P = 0.002) was a statistically significant risk factor associated with cardiac events. CONCLUSION: Obesity is an independent risk factor for trastuzumab-related cardiac toxicity in elderly patients with breast cancer, receiving trastuzumab. Further studies are needed to establish the independent predictive value of obesity on cardiotoxicity in these patients.

Endostatin enhances antitumor effect of tumor antigen-pulsed dendritic cell therapy in mouse xenograft model of lung carcinoma.

OBJECTIVE: To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell (DC)-T cell therapy on lung cancer. METHODS: Transplanted Lewis lung cancer (LLC) models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC-T+endostatin group, DC-T group, and phosphate-buffered saline (PBS) control group. Microvessel density (MVD) of tumor tissue in tumor-bearing mice was determined by immunohistochemistry (IHC). The expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were determined by Western blotting and IHC staining. The proportions of CD8+ T cells, mature dendritic cells (mDC), tumor-associated macrophages [TAM (M1/M2)], and myeloid-derived suppressor cells (MDSC) in suspended cells of tumor tissue were determined by flow cytometry. The expressions of interleukin (IL)-6, IL-10, IL-17, transforming growth factor-ß (TGF-ß) and interferon-γ (IFN-γ) in suspended cells of tumor tissue were detected by enzyme-linked immune sorbent assay (ELISA). RESULTS: DC-T cells combined with endostatin remarkably suppressed tumor growth. MVD of mice in DC-T+endostatin group was significantly lower than that of the control group and DC-T monotherapy group. The expressions of VEGF, IL-6 and IL-17 in tumors were markedly decreased, but IFN-γ and HIF-1α increased after treating with DC-T cells combined with endostatin, compared to control group and DC-T group. In the DC-T+endostatin group, the proportions of MDSC and TAM (M2 type) were significantly decreased, mDC and TAM (M1 type) were up-regulated, and CD8+ T cells were recruited to infiltrate tumors, in contrast to PBS control and DC-T monotherapy. DC-T cells combined with endostatin potently reduced the expressions of IL-6, IL-10, TGF-ß and IL-17 in tumor tissue, and enhanced the expression of IFN-γ. CONCLUSIONS: The study indicated the synergic antitumor effects between endostatin and tumor antigen-pulsed DC-T cells, which may be a prospective therapy strategy to achieve potent antitumor effects on lung cancer.

Stathmin is a potential molecular marker and target for the treatment of gastric cancer.

OBJECTIVE: This study is to investigate the expression levels of stathmin in tissues of gastric cancer, and evaluate the therapeutic effects of stathmin antisense oligodeoxynucleotide (ASODN) and/or docetaxel in human gastric cancer cells. METHODS: Immunohistochemistry was performed to detect the expression levels of stathmin in gastric cancer and adjacent tissues. Stathmin ASODN was transfected into gastric cancer SGC 7901 cell lines. The cell proliferation was assessed with the MTT assay, and the inhibitory rates were calculated. RT-PCR and Western blot analysis were performed to detect the mRNA and protein expression levels of stathmin, respectively. The synergistic effects of stathmin ASODN and docetaxel were evaluated. The efficacy and clinical benefit rates of the treatment of docetaxel combined with stathmin evaluation were investigated and compared. RESULTS: Our results showed that the expression of stathmin was elevated in gastric cancer tissues, indicating a possible association between the stathmin expression and the disease occurrence. The MTT assay and tumor growth experiment revealed that stathmin ASODN significantly inhibited the proliferation of gastric cancer cells, both in vitro and in vivo. Furthermore, stathmin ASDON enhanced the inhibitory effects of docetaxel on the proliferation of gastric cancer cells, indicating a synergistic effect for the combination treatment. Importantly, docetaxel treatment was more effective for stathmin-negative gastric cancer patients, compared with stathmin-positive patients. CONCLUSION: Stathmin expression provides evidence for the treatment planning for gastric cancers. Stathmin might be a potential molecular marker and target for the treatment of gastric cancer.

Relationship between gene polymorphisms of two cytokine genes (TNF-α and IL-6) and occurring of lung cancers in the ethnic group Han of China.

Tumor necrosis factor (TNF) is a cytokine involved in inflammation and TNF-α might be synthesized ectopically in malignant tumors. Interleukin-6 (IL-6) is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. The present study is to investigate the relationship between genetic polymorphisms of the TNF-α and IL-6 genes and susceptibility to lung cancers in the ethnic group Han of North China. The genotypes in the -238G locus of TNF-α gene and the -572C locus of the IL-6 gene were determined by PCR-RFLP method in 138 patients with lung cancers and 138 healthy individuals. Software PHASE 1.0 was used to analyze the experimental data. The non-conditional logistic regression model was used to analyze the statistical association of genotypes and susceptibility in two groups adjusted by multiple factors. We found that the TNF-α and IL-6 polymorphisms may be a critical risk for the genetic susceptibility to lung cancers in the ethnic group Han of North China. SNP polymorphisms at the -238G locus of TNF-α gene and the -572C locus of the IL-6 gene were detected by the RFLP-PCR method. We found that high rates of single-base G-to-A alteration at the -238G locus of both alleles and high rates of single-base C-to-G alteration at the -572C locus of both alleles correlated with occurring of lung cancers. It is possible that the SNP markers at the -238G locus of TNF-α gene and the -572C locus of the IL-6 gene serve as biological markers of lung cancers upon further study in the future.

Efficacy assessment of pemetrexed treatment of an NSCLC case with brain metastasis.

Non-small cell lung cancers (NSCLCs) are among the most common malignancies. Although pemetrexed is often used clinically to cure cancers, its efficacy in NSCLC patients with progressive brain metastases remains unclear. Here, we report a successful NSCLC (adenocarcinoma) case treated with pemetrexed. The detected tumors were treated with 900 mg of pemetrexed disodium (500 mg/m(2)) was administered to the patient on day 1, and 40 mg of cisplatin (25mg/m(2)) was administered on days 1-3, at the interval of 3 weeks. After two cycles of chemotherapy, the brain metastases were reduced. The lesion in the lung was reduced as determined by chest CT-scan. Our results suggest that pemetrexed is an effective therapy for patients with NSCLC and progressive brain metastases.

Correlation of polymorphisms of the vascular endothelial growth factor gene and the risk of lung cancer in an ethnic Han group of North China.

Vascular endothelial growth factor (VEGF) is a potent angiogenic mediator. The present study investigated the relationship between genetic polymorphisms of VEGF and susceptibility to lung cancer in a Han ethnic group of North China. The genotypes in the -2578C and 936C loci of VEGF gene were determined using PCR-RFLP method in 150 patients with lung cancers and 150 healthy individuals. Software PHASE 1.0 was used to analyze the experimental data. The non-conditional logistic regression model was used to analyze the statistical association of genotypes and susceptibility in the two groups adjusted by multiple factors. VEGF polymorphisms were found to be a critical risk for the genetic susceptibility to lung cancers in the ethnic Han group of North China. SNP polymorphisms at the -2578C and 936C loci of the VEGF gene were detected by the RFLP-PCR method. High rates of a single-base C-to-A alteration at the -2578 locus and high rates of a single-base C-to-T alteration at the 936 locus of both alleles were correlated with the occurrence of lung cancer. The SNP markers at the -2578C and 936C loci of the VEGF gene may serve as biological markers of lung cancer.