Chromolaena odorata and Tithonia diversifolia synergistically stimulate kidney erythropoietin and repress cyclin-dependent kinase inhibitors in the bone marrow of Wistar rats

Background: Obesity is considered protective for bone mass, but this view has been progressively challenged. Menopause is characterized by low bone mass and increased adiposity. Our aim was to determine how visceral and bone marrow adiposity change following ovariectomy (OVX), how they correlate with bone quality and if they are influenced by physical activity. Methods: Five-month-old Wistar rats were OVX or sham-operated and maintained in sedentary or physically active conditions for 9 months. Visceral and bone marrow adiposity as well as bone turnover, femur bone quality and biomechanical properties were assessed. Results: OVX resulted in higher weight, visceral and bone marrow adiposity. Visceral adiposity correlated inversely with femur Ct.Th (r = −0.63, p < 0.001), BV/TV (r = −0.67, p < 0.001), Tb.N (r = −0.69, p < 0.001) and positively with Tb.Sp (r = 0.58, p < 0.001). Bone marrow adiposity also correlated with bone resorption (r = 0.47, p < 0.01), bone formation rate (r = −0.63, p < 0.01), BV/TV (r = −0.85, p < 0.001), Ct.Th (r = −0.51, p < 0.0.01), and with higher empty osteocyte lacunae (r = 0.39, p < 0.05), higher percentage of osteocytes with oxidative stress (r = 0.64, p < 0.0.01) and lower femur maximal stress (r = −0.58, p < 0.001). Physical activity correlated inversely with both visceral (r = −0.74, p < 0.01) and bone marrow adiposity (r = −0.92, p < 0.001). Conclusions: OVX increases visceral and bone marrow adiposity which are associated with inferior bone quality and biomechanical properties. Physical activity could contribute to reduce adipose tissue and thereby improve bone quality.

Download Full-text

The Individual Effects of Cyclin-Dependent Kinase Inhibitors on Head and Neck Cancer Cells—A Systematic Analysis

Cancers ◽

10.3390/cancers13102396 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2396

Author(s):

Nina Schoenwaelder ◽

Inken Salewski ◽

Nadja Engel ◽

Mareike Krause ◽

Björn Schneider ◽

...

Keyword(s):

Combination Therapy ◽

Head And Neck ◽

Kinase Inhibitors ◽

In Vivo Studies ◽

Specific Response ◽

Cyclin Dependent Kinase ◽

Systematic Analysis ◽

Mhc I ◽

Oncological Treatment

Cyclin-dependent kinase inhibitors (CDKi´s) display cytotoxic activity against different malignancies, including head and neck squamous cell carcinomas (HNSCC). By coordinating the DNA damage response, these substances may be combined with cytostatics to enhance cytotoxicity. Here, we investigated the influence of different CDKi´s (palbociclib, dinaciclib, THZ1) on two HNSCC cell lines in monotherapy and combination therapy with clinically-approved drugs (5-FU, Cisplatin, cetuximab). Apoptosis/necrosis, cell cycle, invasiveness, senescence, radiation-induced γ-H2AX DNA double-strand breaks, and effects on the actin filament were studied. Furthermore, the potential to increase tumor immunogenicity was assessed by analyzing Calreticulin translocation and immune relevant surface markers. Finally, an in vivo mouse model was used to analyze the effect of dinaciclib and Cisplatin combination therapy. Dinaciclib, palbociclib, and THZ1 displayed anti-neoplastic activity after low-dose treatment, while the two latter substances slightly enhanced radiosensitivity. Dinaciclib decelerated wound healing, decreased invasiveness, and induced MHC-I, accompanied by high amounts of surface-bound Calreticulin. Numbers of early and late apoptotic cells increased initially (24 h), while necrosis dominated afterward. Antitumoral effects of the selective CDKi palbociclib were weaker, but combinations with 5-FU potentiated effects of the monotherapy. Additionally, CDKi and CDKi/chemotherapy combinations induced MHC I, indicative of enhanced immunogenicity. The in vivo studies revealed a cell line-specific response with best tumor growth control in the combination approach. Global acting CDKi’s should be further investigated as targeting agents for HNSCC, either individually or in combination with selected drugs. The ability of dinaciclib to increase the immunogenicity of tumor cells renders this substance a particularly interesting candidate for immune-based oncological treatment regimens.

Download Full-text

Potential of Cyclin-Dependent Kinase Inhibitors as Cancer Therapy

ACS Medicinal Chemistry Letters ◽

10.1021/acsmedchemlett.1c00017 ◽

2021 ◽

Vol 12 (2) ◽

pp. 182-184

Author(s):

Ahmed F. Abdel-Magid

Keyword(s):

Cancer Therapy ◽

Kinase Inhibitors ◽

Cyclin Dependent Kinase

Download Full-text

An Unsuspected Finding of t(9;22): A Rare Case of Philadelphia Chromosome-Positive B-Lymphoblastic Lymphoma

Case Reports in Hematology ◽

10.1155/2017/2413587 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Prajwal Boddu ◽

C. Cameron Yin ◽

Rashmi Kanagal-Shamanna ◽

Guillin Tang ◽

Beenu Thakral ◽

...

Keyword(s):

Bone Marrow ◽

Kinase Inhibitors ◽

Bone Marrow Involvement ◽

Philadelphia Chromosome ◽

Lymphoblastic Lymphoma ◽

Accurate Diagnosis ◽

Biopsy Specimens ◽

B Lymphoblastic Lymphoma ◽

Prophylactic Chemotherapy

While rare, cases of isolated extramedullary disease of B-cell Lymphoblastic Lymphoma (B-LBL) without morphologic bone marrow involvement have been described. In this report, we illustrate the case of an elderly gentleman who presented with isolated testicular and vertebral LBL involvement but had no morphologic bone marrow involvement. The initial plan of treatment was to treat along the lines of Philadelphia negative B-ALL/LBL. During this time, fluorescence in situ hybridization (FISH) and PCR testing for BCR-ABL1 rearrangements were being performed on the marrow specimens as a part of routine diagnostic workup. While the FISH returned negative, PCR testing unexpectedly detected BCR-ABL1 fusion transcripts at a low level of 0.48%. Given their presence, we performed FISH for BCR/ABL1 rearrangement in both testicular and L5 vertebral specimens which were 80–90% positive. He subsequently received rituximab, hyper-CVAD, and dasatinib, along with prophylactic intrathecal prophylactic chemotherapy. The patient achieved a prolonged remission but eventually relapsed, 4 years later. Had it not been for this fortuitous discovery, the patient would not have been treated with tyrosine kinase inhibitors. We emphasize that FISH and PCR testing for BCR-ABL1 rearrangement are integral to arriving at an accurate diagnosis and should be routinely tested on B-LBL biopsy specimens.

Download Full-text

Expression and mutational analysis of Cip/Kip family in early glottic cancer

The Journal of Laryngology & Otology ◽

10.1017/s0022215114003351 ◽

2015 ◽

Vol 129 (2) ◽

pp. 168-173 ◽

Cited By ~ 4

Author(s):

D-K Kim ◽

J H Lee ◽

O J Lee ◽

C H Park

Keyword(s):

Dna Methylation ◽

Polymerase Chain Reaction ◽

Kinase Inhibitors ◽

Mutational Analysis ◽

Glottic Cancer ◽

Cyclin Dependent Kinase ◽

Chain Reaction ◽

Single Strand Conformational Polymorphism ◽

Early Glottic Cancer ◽

Polymerase Chain

AbstractBackground:Genetic alteration of cyclin-dependent kinase inhibitors has been associated with carcinogenesis mechanisms in various organs.Objective:This study aimed to evaluate the expression and mutational analysis of Cip/Kip family cyclin-dependent kinase inhibitors (p21CIP1/WAF1, p27KIP1 and p57KIP2) in early glottic cancer.Methods:Expressions of Cip/Kip family and p53 were determined by quantitative reverse transcription polymerase chain reaction and densitometry. For the analysis of p21 inactivation, sequence alteration was assessed using single-strand conformational polymorphism polymerase chain reaction. Additionally, the inactivation mechanism of p27 and p57 were investigated using DNA methylation analysis.Results:Reduced expression of p27 and p57 were detected in all samples, whereas the expression of p21 was incompletely down-regulated in 6 of 11 samples. Additionally, single-strand conformational polymorphism polymerase chain reaction analysis showed the p53 mutation at exon 6. Methylation of p27 and p57 was detected by DNA methylation assay.Conclusion:Our results suggest that the Cip/Kip family may have a role as a molecular mechanism of carcinogenesis in early glottic cancer.

Download Full-text