INTRODUCTION: Platelet-derived growth factor (PDGF) and its receptor (PDGFR) signaling are key regulators of the tumor microenvironment and they contribute to tumor progression. We evaluated the correlation of PDGF-BB and PDGFR expression with the activation of epithelial-mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC) tissues. METHODS: We evaluated PDGF-BB and PDGFR expression, EMT activity (E-cadherin loss and S100A4 gain in tumor cells), and CAFs (aSMA and S100A4 in stromal cells) via immunohistochemistry analysis of 270 CRC tissues. The expression levels of PDGF-BB/PDGFR, EMT, and CAFs were analyzed in the relation to pathological parameters and disease-free and overall survival times. RESULTS: PDGF-BB in tumor cells and PDGFR in both tumor and stromal cells were expressed. Spindle-shaped stromal cells exhibited expression of both PDGFR and aSMA. PDGFR expression was related to lymphovascular invasion, lymph node metastasis, AJCC stages, and high number of tumor buds. PDGF-BB was weakly related to lymph node metastasis and perineural invasion. PDGFR expression was related with E-cadherin loss and stromal expression of S100A4 and aSMA. PDGF-BB or PDGFR expression was not associated with the disease-free or overall survival time of CRC patients. CONCLUSION: PDGFR expression was related to the activity of CAFs and the EMT process. PDGFR have a crucial role in tumor progression and could be a main target for microenvironment control in CRC treatment.
Human epidermal growth factor receptor-2 (HER2) and 3 (HER3) belong to the epidermal growth factor receptor (EGFR) family of transmembrane receptor tyrosine kinases. In this study, we assessed HER2/HER3 expression levels in specimens of epithelial ovarian cancer and determined their correlation with clinical features of ovarian cancer.
It is well-known that policosanol can improve serum lipid profiles, although the physiological mechanism is still unknown. Here, we investigated functional and structural changes in lipoproteins after consumption of policosanol. To investigate the physiological effect of policosanol, we analyzed serum parameters in young non-smoker (YN; n=7, 24.0±2.4 years), young smoker (YS; n=7, 26.3±1.5 years), and middle-aged subjects (MN; n=11, 52.5±9.8 years) who consumed policosanol daily (10 mg/day) for 8 weeks. After 8 weeks, systolic blood pressure was significantly lowered to 4% (7 mmHg, p=0.022) from initial levels in the YS and MN groups. Moisture content of facial skin increased up to 38 and 18% from initial levels in the YS and MN groups, respectively. Serum triglyceride (TG) levels decreased to 28 and 26% from initial levels in the YN and MN groups, respectively. The percentage of high-density lipoprotein-cholesterol (HDL-C) in total cholesterol was elevated in all subjects (YN, 36%; YS, 35%; MN, 8%) after 8 weeks of policosanol consumption. All groups showed a reduction in serum glucose and uric acid levels. Serum cholesteryl ester transfer protein (CETP) activity was significantly diminished up to 21 and 32% from initial levels in the YN and MN groups, respectively. After 8 weeks, oxidation of the low-density lipoprotein fraction was markedly reduced accompanied by decreased apolipoprotein B (apoB) fragmentation. In the HDL fraction, paraoxonase activity was elevated by 17% along with elevation of apoA-I and cholesterol contents. Electron microscopy revealed that the size and number of HDL particles increased after 8 weeks, and the YS group showed a 2-fold increase in particle size. Daily consumption of policosanol for 8 weeks resulted in lowered blood pressure, reduced serum TG level and CETP activity, and elevated HDL-C contents. These functional enhancements of HDL can prevent and/or attenuate aging-related diseases, hypertension, diabetes and coronary heart disease.
Fertility preservation is an emerging discipline, which is of substantial clinical value in the care of young patients with cancer. Chemotherapy and radiation may induce ovarian damage in prepubertal girls and young women. Although many studies have explored the mechanisms implicated in ovarian toxicity during cancer treatment, its molecular pathophysiology is not fully understood. Chemotherapy may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions. Oxidative stress and the radiosensitivity of oocytes are the main causes of gonadal damage after radiation treatment. Fertility preservation options can be differentiated by patient age, desire for conception, treatment regimen, socioeconomic status, and treatment duration. This review will help highlight the importance of multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.
Although the cancer survival rate has increased, cancer treatments, including chemotherapy and radiotherapy, can cause ovarian failure and infertility in women of reproductive age. Preserving fertility throughout cancer treatment is critical for maintaining quality of life. Fertility experts should propose individualized fertility preservation methods based on the patient's marital status, pubertal status, partner status, and the urgency of treatment. Widely practiced fertility preservation methods, including ovarian transposition and embryo and oocyte cryopreservation, are inappropriate for prepubertal girls or those needing urgent initiation of cancer treatment. Ovarian tissue cryopreservation and transplantation, an emerging new technology, may be a solution for these cancer patients. The use of stem cells in ovarian tissue cryopreservation and transplantation increases oxygenation, angiogenesis, and follicle survival rates. This review discusses the recent advances in ovarian tissue cryopreservation and transplantation with special focus on the use of stem cells to improve fertilization techniques.
Background: To determine the quality of breast milk (BM), we compared the functions of BM from ex-smokers and nonsmokers. Subjects and Methods: We analyzed the contents of lipids, glucose, and protein in BM from ex-smokers (10 cigarettes/day for 13 ± 3 years) as well as infant formula. Results: Nonsmokers' BM showed 2.4- and 1.4-fold higher cholesterol and protein contents, respectively, than BM from smokers. Infant formula contained almost no cholesterol, but did show remarkably higher glucose and triglyceride levels than BM. Microinjection of BM (50 nL) from nonsmokers and smokers into zebrafish embryos resulted in 59% and 44% survival, respectively, whereas formula injection resulted in 31% survival. The higher cholesterol and protein contents of BM were directly correlated with higher embryo survivability, suggesting that cholesterol content is directly and critically associated with growth of neonate infants. Smokers' BM contained smaller-sized apolipoproteinA-I (apoA-I) (24.4 ± 0.2 kDa) than BM from nonsmokers (26.7 ± 0.4 kDa), suggesting that putative modification and cleavage occurred in apoA-I. BM containing higher molecular weight apoA-I resulted in higher embryo survivability. Conclusions: Smoking before pregnancy can affect the composition and quality of BM, resulting in almost complete loss of cholesterol and protein, especially lactoferrin, lactalbumin, and apoA-I, accompanied by proteolytic degradation. These impairment effects of BM are associated with elevation of oxidative stress and lower embryo survivability.
BackgroundSulfadoxine-pyrimethamine (SP) antimalarial therapy has been suggested to potentially increase the birth weight of infants in pregnant women in sub-Saharan Africa, independently of malarial infection. Here, we utilized female intestinal organoid-derived cells cultured within microfluidic Organ Chips to investigate whether SP could directly impact intestinal function and thereby improve the absorption of essential fats and nutrients crucial for fetal growth.MethodsUsing a human organ-on-a-chip model, we replicated the adult female intestine with patient organoid-derived duodenal epithelial cells interfaced with human intestinal endothelial cells. Nutrient-deficient (ND) medium was perfused to simulate malnutrition, resulting in the appearance of enteric dysfunction indicators such as villus blunting, reduced mucus production, impaired nutrient absorption, and increased inflammatory cytokine secretion. SP was administered to these chips in the presence or absence of human peripheral blood mononuclear cells (PBMCs).FindingsOur findings revealed that SP treatment effectively reversed multiple intestinal absorptive abnormalities observed in malnourished female Intestine Chips, as validated by transcriptomic and proteomic analyses. SP also reduced the production of inflammatory cytokines and suppressed the recruitment of PBMCs in ND chips.InterpretationOur results indicate that SP could potentially increase birth weights by preventing enteric dysfunction and suppressing intestinal inflammation. This underscores the potential of SP as a targeted intervention to improve maternal absorption, subsequently contributing to healthier fetal growth. While SP treatment shows promise in addressing malabsorption issues that can influence infant birth weight, we did not model pregnancy in our chips, and thus its usefulness for treatment of malnourished pregnant women requires further investigation through clinical trials.FundingThe Bill and Melinda Gates Foundation, and the Wyss Institute for Biologically Inspired Engineering at Harvard University, and the HDDC Organoid Core of the P30 DK034854.
Purpose: To evaluate radiation sensitivity of dendritic cells in comparison with lymphocytes. Materials and methods: T lymphocytes captured from peripheral blood were irradiated by 0 Gy, 10 Gy, 30 Gy. Apoptosis was measured by flowcytometry for staining of Annexin V 4 hours after irradiation. Immature and mature dendritic cells processed from blood hematopoietic stem cell were irradiated by 0 Gy, 10 Gy, 30 Gy, 100 Gy respectively and apoptosis was measured by flowcytometry with time difference as 4h, 24h and 48h after irradiation. Morphometric analysis by percent nucleus was measured in three cell groups, also. Results: Lymphocytes showed radiation sensitivity by increasing apoptotic fraction according to radiation dose. However, both mature and immature dendritic cells showed consistent fraction of apoptosis in spite of increasing radiation dose. Percent nucleus ratio is significantly higher in lymphocytes than that of mature or immature dendritic cells. Stimulation of T-cell by dendritic cells was not changed after irradiation. Conclusion: Dendritic cells showed radioresistance which was associated with small size of nucleus in comparison with lymphocytes and this result would be used as a basal data of radio-labelling for the cellular trafficking studios in nuclear medicine fields.
Only a few studies have reported the learning curve for sentinel lymph node (SLN) detection in gynecologic malignancies. We investigated the learning curve for SLN detection during robot-assisted laparoscopic surgery for endometrial and cervical carcinomas.This retrospective analysis included patients with stage IA to IIA1 cervical cancer or stage I to III endometrial cancer who underwent SLN mapping using indocyanine green during robot-assisted laparoscopic surgery performed by a single surgeon. Learning curves were analyzed in consecutive cases using SLN detection rates and the cumulative sum (CUSUM) method.SLN mapping was achieved in 81.25% (65/80), 77.50% (62/80), and 66.25% (53/80) of the cases involving the right, left, and simultaneous bilateral pelvic areas, respectively. Learning curve analysis based on the cumulative detection rate showed initial fluctuations followed by stabilization; the time required for proficiency was discordant among the LN regions. However, the CUSUM method showed proficient mapping of the right, left, and bilateral SLNs after 27 to 28 cases.At least 27 cases were required for SLN mapping proficiency in gynecologic cancer; the learning period could influence the surgical quality. Further studies are warranted to confirm the impact of this learning curve on disease outcomes.
Abstract Introduction: Waldenström's macroglobulinemia is a lymphoplasmacytic lymphoma (LPL) associated with a monoclonal immunoglobulin M protein. Although acute kidney injury (AKI) due to immunoglobulin M paraprotein infiltration into the renal interstitium has been reported, there has been no report of AKI with invasion of the immunoglobulin G paraprotein into the renal interstitium in a patient with LPL. Patient concerns: A 65-year-old male was admitted to our hospital with fatigue and decreased renal function. He complained of a 3-kg weight loss in the last 3 months. Diagnosis: The initial blood urea nitrogen and serum creatinine levels were 55.9 and 1.83 mg/dL, respectively. Serum protein electrophoresis revealed a monoclonal component (3.5 g/dL) in the gamma region and immunofixation electrophoresis showed an immunoglobulin G kappa monoclonal protein. Renal pathology revealed that CD3–CD20+ CD138+ lymphoid cells had infiltrated the renal interstitium. A bone marrow biopsy was compatible with LPL. Interventions: Intravenous methylprednisolone (1 mg/kg) was administered after confirming the renal pathological findings. Outcomes: Serum creatinine decreased to 0.8 mg/dL 14 days after treatment Conclusions: Physicians should recognize LPL secreting various immunoglobulins as a possible cause of AKI when renal failure of unknown etiology and serum immunoglobulin paraprotein is present. A kidney biopsy should be performed for definitive diagnosis and appropriate management.
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