Antibody responses to SARS-CoV-2 Omicron infection in patients with hematological malignancies: A multicenter, prospective cohort study.

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.

HIV-associated Burkitt lymphoma in the combination antiretroviral therapy era: Real-world outcomes and prognostication.

We performed a retrospective study to analyze the clinical characteristics and outcomes of human immunodeficiency virus-associated Burkitt's lymphoma in Chongqing University Cancer Hospital, southwest China, from March 2012 to February 2022. In the entire cohort, the median age was 36 years (range, 28-60 years), and more patients were male (82.4%). The median CD4+ T cell count was 214/µl (range, 54-601), of whom 47.1% had a CD4+ T cell count below 200/µl. Most patients had elevated lactate dehydrogenase (LDH), elevated ß2-MG, extranodal involvement and advanced Ann Arbor stage at diagnosis. With a median follow-up of 11.5 months (range, 1.6-94.9 months), the overall 1-year progression-free survival and overall survival (OS) rates were 27.6% and 47.6%, respectively. The 1-year OS times in the LDH < 3 upper limit of normal and LDH ≥ 3 upper limit of normal groups were 62.5% and 31.3%, respectively (p = 0.008). The 1-year OS times in the received <4 cycles and ≥4 cycles groups were 0% and 77.8%, respectively (p < 0.001). These results demonstrated that LDH < 3 upper limit of normal and received ≥4 cycles of chemotherapy were significantly associated with improved outcomes. However, rituximab administration was not significantly associated with improved outcomes.

Clinical characteristics and outcomes of newly diagnosed patients with HIV-associated aggressive B-cell NHL in China.

Little is known about the incidence, clinical characteristics and prognostic factors in HIV associated lymphoma as these are less common than HIV-negative lymphoma in China. Currently, there are no standard guidelines for treatment of these patients. Therefore, we performed a study to analyse the clinical characteristics and outcomes of newly diagnosed HIV-associated aggressive B-cell non-Hodgkin's lymphoma (NHL) patients in Chongqing University Cancer Hospital (CUCH). Totally 86 newly diagnosed HIV-associated aggressive B-cell NHL patients in CUCH, southwest China, from July 2008 to August 2021, were analysed. In the entire cohort, median age was 48 years (range, 23-87 years), and more patients were male (87.2%). Most patients had elevated lactate dehydrogenase (LDH) (82.6%), advanced ann arbor stage (80.2%) and high IPI score (IPI score, 3-5) (62.7%) at diagnosis. Median CD4+ T-cell count at diagnosis was 191/µl (range, 4-1022), 84 patients (97.7%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. In DLBCL patients, cox multivariate analysis showed that age ≥ 60 (HR = 2.251, 95%CI 1.122-4.516; p = 0.012), elevated LDH (HR = 4.452, 95%CI 1.027-19.297; p = 0.041) and received less than two cycles of chemotherapy (HR = 0.629, 95%CI 0.589-1.071; p = 0.012) were independent risk factors for adverse prognosis based on PFS. Age ≥ 60 (HR = 3.162, 95%CI 1.500-6.665; p = 0.002) and received less than two cycles of chemotherapy (HR = 0.524, 95%CI 0.347-0.791; p = 0.002) were also independent risk factor for adverse prognosis based on OS. In BL patients, cox multivariate analysis showed that elevated LDH and received less than two cycles of chemotherapy were independent risk factors for adverse prognosis. In the DLBCL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 12 months, respectively (p = 0.006). Median OS times were not reached and 36 months, respectively (p = 0.021). In the BL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 4.8 months, respectively (p = 0.046). Median OS times were not reached and 10.1 months, respectively (p = 0.035). Overall, these data indicated that standardized anti-lymphoma therapy and rituximab administration were significantly associated with improved outcomes in patients with HIV-associated DLBCL and BL.

Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. The development of immunotherapy greatly improves the patient prognosis but there are some exceptions. Thus, screening for better biomarkers for prognostic evaluation could contribute to the treatment of DLBCL patients. AIM: To screen the novel mediators involved in the development of DLBCL. METHODS: The GSE60 dataset was applied to identify the differentially expressed genes (DEGs) in DLBCL, and the principal components analysis plot was used to determine the quality of the included samples. The protein-protein interactions were analyzed by the STRING tool. The key hub genes were entered into to the GEPIA database to determine their expressions in DLBCL. Furthermore, these hub gene alterations were analyzed in cBioportal. The UALCAN portal was employed to analyze the expression of the hub genes in different stages of DLBCL. The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Score was conducted to evaluate the correlation between the gene expression and tumor purity. The gene-gene correlation analysis was conducted in the GEPIA. The stromal score analysis was conducted in TIMER to confirm the correlation between the gene expression and infiltrated stromal cells. The correlation between the indicated genes and infiltration level of cancer-associated fibroblasts (CAFs) was also completed in TIMER with two methods, MCP-Counter and Tumor immune dysfunction and exclusion. The correlation between fibronectin (FN1) protein level and secreted protein acidic and cysteine-rich (SPARC) messenger ribonucleic acid expression was confirmed in the cBioportal. RESULTS: The top 20 DEGs in DLBCL were identified, and the principal components analysis plot confirmed the quality of the significant DEGs. The pairwise correlation coefficient analysis among all samples showed that these DEGs have a certain co-expression pattern. The DEGs were subjected to STRING to identify the hub genes, alpha-2-macroglobulin (A2M), cathepsin B (CTSB), FN1, matrix metallopeptidase 9 (MMP9), and SPARC. The five hub genes were confirmed to be overexpressed in DLBCL. The cBioportal portal detected these five hub genes that had gene alteration, including messenger ribonucleic acid high amplification and missense mutation, and the gene alteration percentages of A2M, FN1, CTSB, MMP9, and SPARC were 5%, 8%, 5%, 2.7%, and 5%, respectively. Furthermore, the five hub genes had a potential positive correlation with tumor stage. The correlation analysis between the five genes and tumor purity confirmed that the five genes were overexpressed in DLBCL and had a positive correlation with the development of DLBCL. More interestingly, the five genes had a significant correlation with the stromal infiltration scores. The correlation analysis between the fives genes and CAFs also showed a significant value, among which the top two genes, FN1 and SPARC, had a remarkable co-expression pattern. CONCLUSION: The top DEGs were identified, and the five hub genes were overexpressed in DLBCL. Furthermore, the gene alterations were confirmed and the positive correlation with tumor purity revealed the overexpression of the five genes and close association with the development of DLBCL. More interestingly, the five genes were positively correlated with stromal infiltration, especially in CAFs. The top two genes, FN1 and SPARC, showed a co-expression pattern, which indicates their potential as novel therapeutic targets for DLBCL.

miR-744-5p Inhibits Multiple Myeloma Proliferation, Epithelial Mesenchymal Transformation and Glycolysis by Targeting SOX12/Wnt/ß-Catenin Signaling.

PURPOSE: This study investigated the function and molecular mechanisms of miR-744-5p in multiple myeloma (MM). METHODS: miR-744-5p and SRY-related high-mobility-group box 12 (SOX12) expression in clinical tissues and MM cells was monitored by quantitative real-time polymerase chain reactions and Western blot. miR-744-5p expression in MM cells was regulated by transfection. Cell proliferation was researched by cell counting kit-8 assay and plate clone formation experiment. Transwell experiment was utilized for migration and invasion detection. Glycolysis test was conducted for the detection of glucose uptake and lactate production of MM cells. The relationship between miR-744-5p and SOX12 was determined by dual-luciferase reporter gene assay and RNA pull-down experiment. In vivo experiment was conducted using nude mice. RESULTS: miR-744-5p expression was reduced in MM patients (P<0.01). Low miR-744-5p expression was associated with lower 60-month survival in MM patients (P=0.0402). miR-744-5p overexpression inhibited MM cells proliferation, invasion, migration, glucose uptake, lactate production, and epithelial mesenchymal transformation (EMT) (P<0.01). miR-744-5p directly inhibited SOX12 expression. miR-744-5p silencing promoted MM cells proliferation, invasion, migration, glucose uptake, lactate production, and EMT by elevating SOX12 (P<0.01). miR-744-5p inhibited the growth of MM xenograft tumors in vivo (P<0.001). CONCLUSION: miR-744-5p inhibits MM cells proliferation, invasion, migration, EMT, and glycolysis by targeting SOX12/Wnt/ß-catenin.

Sintilimab as salvage treatment in an HIV patient with relapsed/refractory Hodgkin: a case report.

The prognosis of relapsed/refractory classical Hodgkin lymphoma companied with Human immunodeficiency virus (R/R HIV-cHL) is poor due to insufficient effective treatments. Nowadays, immune checkpoint blockade is an important new treatment option for patients with relapsed/refractory classical Hodgkin lymphoma (cHL), but rare cases have been reported in R/R HIV-cHL. We present a case of R/R HIV-cHL young patient, who has been successfully treated with sintilimab without significant side effects. In May 2018, we received an Hodgkin lymphoma companied with Human immunodeficiency virus (HIVcHL) patient. At first, we gave him ABVD regime chemotherapy. In April 2019, after 6 cycles of ABVD and radiation, we evaluated the effect of treatment and found that the disease actually progressed. The patient refused auto stem cell transplant, so the second line GDP regime chemotherapy was administrated. After five cycles of the treatment, in September 2019, a PET-CT examination found a new emerging enlargement lymph node in the retroperitoneum and with an elevated SUV. In October 2019, after obtaining the patient's consent, we gave him PD-1 immune checkpoint treatment. And 9 cycles later, PET-CT showed that the enlargement lymph node found last time in the retroperitoneum had disappeared completely, with no other lesions were found. All the courses of treatment went through smoothly, and no severe toxicity happened. Immune checkpoint blockade is successful in R/R HIV-cHL, the toxicities are mild and accepted.

Body Mass Index and Primary Headache: A Hospital-Based Study in China.

OBJECTIVE: Primary headache and obesity are highly prevalent disorders in the general population. Although many studies have reported an association between the two, there is still no overall comprehension about this relationship. To gain a more accurate understanding in this regard, we analyzed data from a 2011 cross-sectional study in Chongqing, China. METHODS: Patients with a chief complaint of headache were administered a headache questionnaire and diagnosed by neurology doctors in accordance with the International Classification of Headache Disorders 2nd Edition (ICHD-II) criteria. Patients aged < 18 years or diagnosed with secondary headache were excluded. RESULTS: Of 1327 patients who cited headache as the chief complaint, 16 were excluded for missing data, while 396 were diagnosed with chronic headache (177 chronic migraine [CM], 186 chronic tension-type headache [CTTH], and 33 other chronic headache) and 915 with episodic headache (369 episodic migraine [EM], 319 episodic tension-type headache [ETTH], and 227 other episodic headache). Chronic headache patients had a higher number of headache days per month, longer duration of headache history, and greater tendency to overuse analgesics than episodic headache patients. The CM and ETTH patients were more apt to be overweight and had a significantly greater body mass index (BMI; p < 0.05) than the EM and CTTH patients. Overweight (odds ratio [OR] = 3.64; 95% confidence interval (CI), 1.19-8.81) and obesity (OR = 28.63; 95% CI, 2.96-276.6) were independently associated with CM but not with other headaches, and this association was not influenced by other factors such as medication overuse. CONCLUSIONS: The relationship between headache and overweight/obesity varies depending on the type of primary headache. CM patients are more likely to have a higher body mass index than EM patients, while ETTH patients are more likely to be overweight/obese than CTTH patients.

The Signal Transducer and Activator of Transcription 5B (STAT5B) Gene Promotes Proliferation and Drug Resistance of Human Mantle Cell Lymphoma Cells by Activating the Akt Signaling Pathway.

BACKGROUND Mantle cell lymphoma (MCL) is a high-grade B-cell lymphoma with poor prognosis. Fludarabine is used alone or in combination for relapsed and advanced-stage MCL. The expression of the signal transducer and activator of transcription 5B (STAT5B) gene is associated with tumorigenesis in solid tumors, but its role in MCL remains unknown. The aims of this study were to investigate the role of STAT5B in GRANTA-519 human mantle cell lymphoma cells and drug resistance. MATERIAL AND METHODS GRANTA-519 human mantle cell lymphoma cells were cultured with and without 10 µM fludarabine dephosphorylated 9-ß-D-arabinofuranosyl-2-fluoroadenine, (2-F-araA) or 10 µM 4-hydroperoxycyclophosphamide (4-HC). The MTT assay assessed cell proliferation. Flow cytometry was used to investigate the cell cycle in MCL cells treated with the specific inhibitor of the Akt pathway, LY294002, and assessed cell cycle and cell apoptosis. Western blot was used to detect the expression levels of p-Akt/Akt and STAT5B/p-STAT5B. The gene expression profiles of lymph node (LN)-derived MCL cells were compared with peripheral blood (PB)-derived lymphocytes using bioinformatics and hierarchical cluster analysis. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to determine the expression of the marker of proliferation Ki-67 (MKI67) gene. RESULTS STAT5B was significantly upregulated in LN-derived MCL cells compared with PB lymphocytes. Increased expression of STAT5B was associated with increased MCL cell proliferation and reduced cell apoptosis and was associated with drug resistance and activation of Akt. CONCLUSIONS STAT5B promoted cell proliferation and drug resistance in human MCL cells by activating the Akt signaling pathway.

Long intergenic noncoding RNA-p21 inhibits apoptosis by decreasing PUMA expression in non-small cell lung cancer.

OBJECTIVE: Long noncoding RNAs (lncRNAs) are important mediators in tumor progression. Long intergenic noncoding RNA-p21 (lincRNA-p21) participates in multiple biological processes. This study explored the role of lincRNA-p21 in human non-small cell lung cancer (NSCLC) progression and potential regulatory mechanisms. METHODS: LincRNA-p21 expression in NSCLC tissues and cell lines (A549, H1299, H1650, and NCI-H2087) was determined by quantitative real-time PCR. LincRNA-p21 overexpressing and sh-lincRNA-p21 lentiviral were respectively transfected into H1299 and A549 cells. Flow cytometry was used to measure apoptosis. Microarray analysis and RNA pull-down assay were used to predict the target genes of lincRNA-p21. Finally, PUMA siRNA and overexpressing PUMA were transfected into NSCLC cells, and the extent of cell apoptosis was measured. The protein expression levels of the relative genes were confirmed by western blot analysis. RESULTS: LincRNA-p21 was significantly upregulated in NSCLC tissues and cells. The upregulation of lincRNA-p21 considerably inhibited cell apoptosis while the downregulation of lincRNA-p21 showed the opposite effect. PUMA was a direct target gene of lincRNA-p21 and was negatively correlated with lincRNA-p21 in NSCLC specimens. The anti-apoptotic effect of lincRNA-p21 can be effectively attenuated by the upregulation of PUMA. CONCLUSION: LincRNA-p21 is aberrantly upregulated in NSCLC and inhibits cell apoptosis by decreasing PUMA expression.

Co-culture of dendritic cells and cytokine-induced killer cells effectively suppresses liver cancer stem cell growth by inhibiting pathways in the immune system.

BACKGROUND: Application of dendritic cells (DC) for cancer immunotherapy involves tumor-associated immunogenic antigens for effective therapeutic strategies. The present study investigated whether DC co-cultured with autologous cytokine-induced killer cells (CIK) could induce a more specific immune response against liver cancer stem cells (LCSC) generated from human hepatocellular carcinoma (HCC) cells in vitro and in vivo. METHODS: Human DC and CIK were generated from peripheral blood mononuclear cells (PBMCs) taken from consenting liver cancer patients. Flow cytometry was used to determine the phenotypes of DC and CIK, and cell proliferation. The tumor growth and anti-tumor activity of these cells were further evaluated using a nude mouse tumor model. RESULTS: We demonstrated that DC and CIK significantly enhanced the apoptosis ratio, depending on DC-CIK cell numbers, by increasing caspase-3 protein expression and reducing proliferating cell nuclear antigen (PCNA) protein expression against LCSC. The in vivo data indicated that DC-CIK exhibited significant LCSC cell-induced tumor growth inhibition in nude mice, which was most significant with LCSC antigen loaded DCs. CONCLUSIONS: The results showed, that DC-CIK cells could inhibit HCC and LCSC growths in vitro and in vivo and the most successful DC triggering of cell cytotoxic activity could be achieved by their LCSC antigen loading.

KIF26B promotes cell proliferation and migration through the FGF2/ERK signaling pathway in breast cancer.

BACKGROUND: Many studies have suggested that high KIF26B expression is directly linked to poor prognostic outcomes in breast cancer. However, the exact role of KIF26B in breast cancer progression is not fully understood. In this study, we aimed to explore the function and mechanism of KIF26B in breast cancer progression. METHODS: Quantitative real-time PCR and immunohistochemistry analysis were used to detect KIF26B expression in breast cancer cell lines and patient samples. Cell proliferation was assessed by CCK-8 assay, and cell migration and invasion were evaluated by wound healing assay and transwell assay. Western blot analysis was carried out to assess the underlying molecular mechanisms. Tumor formation and metastasis were determined by in vivo mouse experiments. RESULTS: KIF26B levels were significantly increased in breast cancer cells and patient samples. KIF26B level correlated with tumor size, TNM grade, and differentiation in patients with breast cancer. Overexpressing KIF26B in vitro promoted breast cancer cell proliferation and migration by activating FGF2/ERK signaling, while silencing KIF26B had the opposite effects. Similarly, KIF26B knockdown repressed tumor formation and metastasis in nude mice. CONCLUSION: KIF26B promoted the development and progression of breast cancer and might act as a potential therapeutic target for treating breast cancer.