Correlation Between β2-Microglobulin, Grobulin Levels & The Number of Plasmatic Cells in Patients with Multiple Myeloma

Introduction: Multiple myeloma is multifocal neoplasia of plasmatic cells that affects the bone marrow. It is associated with the production of a urinary or serum protein. It represents approximately 1 percent of cancer cases worldwide and between 10 to 15 percent of all cases of hematological malignancy. Furthermore, it has been proposed that the β2-microglobulin levels are correlated with other factors that can predict multiple myelomas such as the number of plasmatic cells and the creatine levels. Goals: To determine the correlation between β2-microglobulin, globulin levels, and the number of plasmatic cells in patients with multiple myeloma. Methods and techniques: We conducted an observational, retrospective, transversal, and analytical study in the Hospital of the Mexican Institute of Social Security at the Veracruz port. Our population analyzed comprehended 45 patients between the ages 30 and 80 with a confirmed diagnosis of multiple myeloma. We measured the β2-microglobulin levels and globulin levels, and the number of plasmatic cells during the diagnosis of patients. Furthermore, we conducted a statistical analysis using a Pearson correlation. Results: The average age was 61 years with a margin of error of 11.48 years. The myeloma of IgG type was the one of major prevalence and represent 82.2 percent. It was followed by the IgA type and the IgM type, which represented 15.5 and 2.2 percent respectively. The Pearson correlation coefficient (Pearson's r) between the β2-microglobulin levels and globulin levels was 0.92. The Pearson's r between the number of plasmatic cells and β2-microglobulin, excluding patients with high serum creatine levels (i.e. larger than 1.2 mg/dl), was 0.371. Conclusions: The predominant type of myeloma in the analyzed population was the IgG type. Furthermore, this myeloma affected mainly men in our study. The average age was 61 years with a margin of error of 11.48 years when compared to other populations in our study.

Excess body weight association with various cancer: A United States population-based study 2021.

e18558 Background: Excess body weight (EW) is a rising healthcare issue affecting over two-thirds of the United States (US) population, and it is a risk factor for various cancer. Methods: We used Explorys, IBM, a US database that includes ̃ 73 million patients. We evaluated non-gastrointestinal cancers prevalence based on age (18-64 and ≥ 65 years; for female cancers 18-49 and ≥ 50 years), race; Caucasians (C) and African-Americans (AA), and weight; normal weight (N) with BMI 18.5- 24.9 kg/m2 and EW for BMI ≥ 25 kg/m2. Compared to NW, the odds ratio (OR) and 95% confidence interval (CI) for multiple cancer rates in the EW group were calculated. p-value of <0.001 was considered significant (S) and > 0.001 as non-significant (NS). Results: A population of 26.9 million was included. C 85.6%, AA 14.4%. See table. Conclusions: A strong association between EW and urological cancers (prostate, bladder, renal), non-Hodgkin's lymphoma, multiple myelomas (MM), breast cancer, endometrial cancer, ovarian cancer in C 18-64 yrs but not in C ≥ 65 yrs with the exception for kidney cancer. A similar finding in AA 18-64 yrs for cancers of prostate, renal, breast, uterus, and MM compared to AA ≥ 65 yrs. EW is possibly more oncogenic earlier in life, especially in C.[Table: see text]

CRISPR-edited CART with GM-CSF knockout and auto secretion of IL6 and IL1 blockers in patients with hematologic malignancy

Revolutionary CART therapy still faces the challenge of severe cytokine release syndrome (CRS). While IL6 and IL1 have been demonstrated as essential contributors, GM-CSF is one of the most abundant inflammatory cytokines secreted by CART and has also been suggested in contributing to CRS. To minimize GM-CSF production from CART to reduce its associated toxicity, we conducted a pilot study (ChiCTR2000032124) of CRISPR-edited GM-CSF knockout (KO) in CART secreting anti-IL6 scFv and IL1RA, with additional TCR KO for tracing edited CART. The initial results of three patients (1 Non-Hodgkin lymphoma (NHL) and 2 multiple myelomas (MMs)) are summarized as: 3/3 complete response, 2/3 none CRS, 1/3 grade 2 CRS, and 0/3 neurotoxicity. The analysis revealed low levels of GM-CSF, IL6 and IL1B at the time of interferon-gamma (IFNG) peaks, and elevated IL1RA. We also observed significant expansion of CD3– CART during treatment and no aberrant expansion of CD3– CART in the follow-up. Re-expansion of CD3– CART was observed in two patients while recurring CD19+ cells were eradicated in the patient with NHL. In summary, our study supported the safety and durable potency of CRISPR-edited CART in patients, providing a novel platform for developing autologous or allogeneic CART to minimize GM-CSF-associated toxicity in addition to autonomous IL6/IL1 blockade.

Light Chain Predominant Intact Immunoglobulin Monoclonal Gammopathy Disorders: Shorter Survival in Light Chain Predominant Multiple Myelomas

Background A proportion of intact immunoglobulin (Ig)–producing multiple myelomas (MMs) was observed to secrete much higher amounts of free light chains (LCs) than usual. Objectives To determine the change point between usual and LC-predominant intact Ig-secreting MMs and other monoclonal gammopathic manifestations and the biological significance of the observation. Methods We conducted retrospective examination of laboratory findings in 386 MM, 27 smoldering MM, and 179 monoclonal gammopathy of undetermined significance (MGUS) cases that secreted intact Igs. We recorded the highest levels of involved serum free LC, highest ratio of involved to uninvolved LC, highest concentration of involved LC per g of monoclonal Ig, and highest value for ratio of involved to uninvolved LCs divided by the monoclonal Ig concentration. Each data set was sorted into kappa- and lambda LC-associated lesions. Length of time, in months, between diagnosis and last contact with the patients having myeloma was recorded. Results Change point analysis of data revealed a subgroup of cases with distinctly higher levels of free LCs. In myelomas, including plasma cell leukemias, 16.4% of myelomas with kappa LCs and 22.3% of myelomas with lambda LCs, the LC secretion was distinctly higher than in the remaining cases, by a combination of 4 parameters, listed herein. Corresponding figures for smoldering myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) were 12.5, 27.3, 3.8, and 6.8, respectively. Ten of the 13 (77%) cases of plasma cell leukemia) and all cases of IgD myeloma (n = 4) showed excess secretion of serum free LCs. Among IgG and IgA myelomas, including plasma cell leukemias, the LC-predominant lesions had shorter survival, by an average of 22.5 months. Conclusions In total, 18.4% of MMs, including plasma cell leukemias, secrete distinctly higher amounts of serum free LCs than other intact Ig-secreting myelomas and confer significantly lower survival. Quantification of monoclonal serum free LCs may be useful in this subgroup in monitoring progress and potentially in ascertaining minimal residual disease. The findings also stress the need for separate criteria for kappa and lambda LC associated monoclonal gammopathic manifestations. The significantly shorter survival of patients with LC-predominant myelomas warrants consideration in prospective trials of treatments.

Chemopreventive Property of Sencha Tea Extracts towards Sensitive and Multidrug-Resistant Leukemia and Multiple Myeloma Cells

The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on sensitive and multidrug-resistant leukemia and a panel of nine multiple myelomas (MM) cell lines. We found that sencha extracts induced cytotoxicity in leukemic cells and MM cells to different extents, yet its effect on normal cells was limited. Furthermore, sencha extracts caused G2/M and G0/G1 phase arrest during cell cycle progression in CCRF/CEM and KMS-12-BM cells, respectively. Specifically, sencha-MeOH/H2O extracts induced apoptosis, ROS, and MMP collapse on both CCRF/CEM and KMS-12-BM cells. The analysis with microarray and COMPARE in 53 cell lines of the NCI panel revealed diverse functional groups, including cell morphology, cellular growth and proliferation, cell cycle, cell death, and survival, which were closely associated with anti-tumor effects of sencha tea. It is important to note that PI3K/Akt and NF-κB pathways were the top two dominant networks by ingenuity pathway analysis. We demonstrate here the multifactorial modes of action of sencha tea leading to chemopreventive effects of sencha tea against cancer.

Oridonin Improves the Sensitivity of Multiple Myeloma Cells to Bortezomib through the PTEN/PI3K/Akt Pathway

Bortezomib is an effective drug for the treatment of multiple myelomas. However, its long-term effectiveness is limited by the development of drug resistance. Oridonin, a natural diterpenoid purified from Rabdosia rubescens, has the potential to diminish resistance to bortezomib. To examine the mechanism underlying the diminution of bortezomib-resistance in multiple myeloma by oridonin, we have created a bortezomib-resistant cell line of multiple myeloma cells (RPMI-8226R). Using MTT assay, apoptosis assays and western blot analysis, we evaluated and compared the effects of oridonin on the cell viability, proliferation, apoptosis, and protein expression levels in bortezomib-resistant (RPMI-8226R) and bortezomib-sensitive (RPMI-8226) myeloma cells. The results show that oridonin sensitized multiple myeloma cells leading to increased apoptosis rate via regulating the PTEN/PI3K/AKT pathway. Furthermore, oridonin activated the expression of PTEN, which is a negative regulator of the PI3K/AKT pathway, while inhibitinged the expression of p-Akt. These results demonstrated that oridonin might be a useful natural compound in bortezomib-resistant multiple myeloma treatment.

Osteonecrosis of the maxilaries associated with use of biphosphonate

Introduction: Bisphosphonates (BF) are inhibitors of reabsorption bone and are indicated for the treatment of Osteoporosis, Bone Metastasis, Multiple Myelomas and Paget's Disease. They are pyrophosphate analogs, which have high affinity for bone tissue inhibiting the action of osteoclasts. Although it has benefits for patients with of such diseases by assisting, for example, in the pain control prolonged use may lead to osteonecrosis of the jaws. Objectives: This article aims to review themedical literature on the use of bisphosbonates and dental surgeries. Materials and Methods: The indexed articles google academico and PubMed were scanned and the articles with the highest impact factor were selected. Results: We found 350 articles and selected 20 with the highest impact factor. Conclusion: Bisphosphonates are substances that can cause oteonecrosis in patients undergoing invasive dental treatments. KEY WORDS: Osteonecrosis, bisphosphonate, necrosis of the jaws