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1.
Clin Lab ; 67(9)2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34542963

ABSTRACT

BACKGROUND: COVID-19 caused by SARS-CoV-2 has been inducing an ongoing global health and economic emergency. Although viral pneumonia is the most striking presentation for COVID-19 patients, it has been noticed that some patients may also be accompanied with an abnormal liver function. METHODS: CT was performed in both lungs, and routine bloodwork and the blood metabolic panel were measured. RESULTS: Here, we report on a young male patient without any history of live diseases who suffered simultaneously both SARS-CoV-2 caused pneumonia and hepatitis as evidenced by increased serum bilirubin together with increased serum transaminases. CONCLUSIONS: Studies on mechanisms whereby SARS-CoV-2 causing liver damages might provide more information about the pathogenesis of COVID-19 and help management of this global health emergency.


Subject(s)
COVID-19 , Liver Diseases , Pneumonia, Viral , Humans , Male , Pneumonia, Viral/diagnosis , SARS-CoV-2
2.
BMC Pulm Med ; 21(1): 223, 2021 Jul 12.
Article in English | MEDLINE | ID: mdl-34247594

ABSTRACT

BACKGROUND: Ciliated muconodular papillary tumor (CMPT) is an incredibly rare pulmonary tumor. Currently, little is known about CMPT, and it has not yet been classified by the World Health Organization. The clinical manifestation of CMPT is nonspecific and the diagnosis is only based on pathology. CMPT has been documented in limited reports as a benign tumor, thus the treatment is typically with surgical excision if a solid tumor is identifiable. The prognosis of CMPT is very positive, as no recurrence has been reported in the limited literature available. However, CMPT accompanied with adenocarcinoma in situ has not been reported previously in the literature. CASE PRESENTATION: In this report, we presented a case of a 53-year-old male smoker with CMPT associated with adenocarcinoma in situ. This diagnosis was confirmed by pathological examination, including immunohistostaining. No solid resectable lesion was identified on CT scan; therefore, no surgery was performed. The patient's adenocarcinoma in situ was disseminated in both lungs, thus chemotherapeutic treatment with cisplatin and pemetrexed was given. The patient will be continually followed up closely on a wait-and-watch basis. CONCLUSIONS: In summary, our report reveals a unique case of CMPT in conjunction with adenocarcinoma in situ, potentially revealing an association between CMPT and malignancy which has not been previously reported. More similar case studies will be beneficial to determine the authentic relationship between CMPT and adenocarcinoma in situ.


Subject(s)
Adenocarcinoma in Situ/pathology , Carcinoma, Papillary/pathology , Lung Neoplasms/pathology , Adenocarcinoma in Situ/diagnostic imaging , Antineoplastic Agents/therapeutic use , Carcinoma, Papillary/drug therapy , Cisplatin/therapeutic use , Humans , Lung Neoplasms/drug therapy , Male , Middle Aged , Pemetrexed/therapeutic use , Tomography, X-Ray Computed , Treatment Outcome
3.
Clin Lab ; 66(1)2020 Jan 01.
Article in English | MEDLINE | ID: mdl-32013360

ABSTRACT

BACKGROUND: Nocardia infection is a very rare bacterial infection caused by Gram-positive, aerobic nocardia species. However, in recent years, it has become a serious infection in immunocompromised patients. Earlier diagnosis plays a pivotal in the effective treatment of nocardia infection. METHODS: In this study, we reported a 65-year-old male patient with nephrotic syndrome who had disseminated abscesses in the lungs, right lower limb, and right cheek. RESULTS: Bacterial culture from these lesions confirmed the presence of nocardia. Timely administration of sensitive antibiotics resulted in a quick recovery for this patient. CONCLUSIONS: Nocardia infection should be considered in the differential diagnosis of infectious lesions, especially when a patient has multiple abscesses and an underlying disorder in which the immune function of the patient may be compromised.


Subject(s)
Nephrotic Syndrome/complications , Nocardia Infections , Aged , Humans , Immunocompromised Host , Lung Abscess , Male , Nocardia , Skin Diseases, Bacterial
4.
Int J Cancer ; 144(10): 2516-2528, 2019 05 15.
Article in English | MEDLINE | ID: mdl-30415472

ABSTRACT

It is now widely accepted that mitochondrial biogenesis is inhibited in most cancer cells. Interestingly, one of the possible exceptions is colorectal cancer (CRC), in which the content of mitochondria has been found to be higher than in normal colon mucosa. However, to date, the causes and effects of this phenomenon are still unclear. In the present study, we systematically investigated the functional role of mitochondrial single-strand DNA binding protein (mtSSB), a key molecule in the regulation of mitochondrial DNA (mtDNA) replication, in the mitochondrial biogenesis and CRC cell growth. Our results demonstrated that mtSSB was frequently upregulated in CRC tissues and that upregulated mtSSB was associated with poor prognosis in CRC patients. Furthermore, overexpression of mtSSB promoted CRC cell growth in vitro by regulating cell proliferation. The in vivo assay confirmed these results, indicating that the forced expression of mtSSB significantly increases the growth capacity of xenograft tumors. Mechanistically, the survival advantage conferred by mtSSB was primarily caused by increased mitochondrial biogenesis and subsequent ROS production, which induced telomerase reverse transcriptase (TERT) expression and telomere elongation via Akt/mTOR pathway in CRC cells. In addition, FOXP1, a member of the forkhead box family, was identified as a new transcription factor for mtSSB. Moreover, our results also demonstrate that proinflammatory IL-6/STAT3 signaling facilitates mtSSB expression and CRC cell proliferation via inducing FOXP1 expression. Collectively, our findings demonstrate that mtSSB induced by inflammation plays a critical role in the regulation of mitochondrial biogenesis, telomerase activation, and subsequent CRC proliferation, providing a strong evidence for mtSSB as drug target in CRC treatment.


Subject(s)
Cell Proliferation/genetics , Colorectal Neoplasms/genetics , DNA-Binding Proteins/genetics , Interleukin-6/genetics , Mitochondria/genetics , Mitochondrial Proteins/genetics , Telomerase/genetics , Up-Regulation/genetics , Cell Line, Tumor , DNA, Mitochondrial/genetics , Humans , Organelle Biogenesis , STAT3 Transcription Factor , Signal Transduction/genetics , Transcriptional Activation/genetics
5.
Clin Lab ; 65(3)2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30868844

ABSTRACT

BACKGROUND: Primary hepatic tuberculosis is a very rare clinical form of tuberculosis, with atypical clinical presentations and nonspecific imaging features. This results in great difficulty to reach a correct and timely clinical diagnosis. Traditionally, liver biopsy is the gold standard for its diagnosis. Here we assessed the effectiveness of using a T-SPOT.TB test in the early diagnosis of primary hepatic tuberculosis. METHODS: We report a case of primary hepatic tuberculosis whose location of hepatic lesion renders it hard to perform a biopsy. Instead, a T-SPOT.TB test was utilized to help in the early diagnosis of this rare form of tuberculosis. A conventional fourdrug regimen for anti-tubercular therapy together with vitamin B6 was initiated and maintained for 6 months. RESULTS: The T-SPOT.TB test was highly positive for ESAT-6 (87 > 20) and CFP-10 (89 > 20). Dull pain in the upper right abdomen was gone 2 months post treatment. The abnormal lesions shown in an MRI reduced significantly 4 months post treatment. Spot count for ESAT-6 and CFP-10 decreased 6 months post treatment. CONCLUSIONS: The results of this study suggest the critical role of T-SPOT.TB test in the earlier diagnosis of prima¬ry hepatic tuberculosis for those patients who have difficulties having a hepatic biopsy.


Subject(s)
Tuberculosis, Hepatic/diagnosis , Antigens, Bacterial/analysis , Bacterial Proteins/analysis , Female , Humans , Young Adult
6.
Cereb Cortex ; 27(5): 2941-2954, 2017 05 01.
Article in English | MEDLINE | ID: mdl-27226442

ABSTRACT

The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh-driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.


Subject(s)
Body Patterning/physiology , Cell Differentiation/physiology , Models, Biological , Prosencephalon/physiology , Signal Transduction/physiology , Cell Line , Cells, Cultured , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Embryonic Stem Cells , Gene Expression Regulation, Developmental/physiology , Humans , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Prosencephalon/cytology , Prosencephalon/embryology , RNA, Messenger/metabolism , Time Factors , Transfection
7.
Cell Immunol ; 304-305: 16-26, 2016.
Article in English | MEDLINE | ID: mdl-27173733

ABSTRACT

IFN-γ(-/-) NOD.H-2h4 mice develop autoimmune disease with extensive hyperplasia and proliferation of thyroid epithelial cells (TEC H/P) and fibrosis. Splenic T cells from donors with severe TEC H/P transfer TEC H/P to SCID recipients. The goal of this study was to determine what factors control TEC H/P development/progression by examining T cells, markers of apoptosis, senescence and proliferation in thyroids of SCID recipients over time. At 28days, T cell infiltration was maximal, thyrocytes were proliferating, and fibrosis was moderate. At days 60 and 90, thyroids were larger with more fibrosis. T cells, cytokines and thyrocyte proliferation decreased, and cell cycle inhibitor proteins, and anti-apoptotic molecules increased. T cells and thyrocytes had foci of phosphorylated histone protein H2A.X, indicative of cellular senescence, when TEC H/P progressed and thyrocyte proliferation declined. Some thyrocytes were regenerating at day 90, with irregularly shaped empty follicles and ciliated epithelium. Proliferating thyrocytes were thyroid transcription factor (TTF1)-positive, suggesting they derived from epithelial cells and not brachial cleft remnants.


Subject(s)
Histones/metabolism , T-Lymphocytes/immunology , Thyroid Epithelial Cells/metabolism , Thyroid Gland/pathology , Thyroiditis, Autoimmune/metabolism , Animals , Cell Differentiation , Cell Proliferation , Cells, Cultured , Cellular Senescence , Cytokines/metabolism , DNA-Binding Proteins/metabolism , Disease Models, Animal , Fibrosis , Humans , Hyperplasia , Interferon-gamma/genetics , Mice , Mice, Knockout , Mice, SCID , Thyroid Epithelial Cells/pathology , Thyroiditis, Autoimmune/pathology , Transcription Factors
8.
J Surg Oncol ; 113(4): 364-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27100023

ABSTRACT

BACKGROUND: Interleukin-32 (IL-32) is a recently recognized intracellular, proinflammatory cytokine which may play a role in cancer metastasis and patient survival. The role of IL-32 in cancer, especially its direct effect on cancer cells, is not well understood. MATERIAL AND METHODS: Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining, and caspase-3 activity assay were used to investigate the in vitro role for IL-32α in human melanoma growth. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. RESULTS: Exogenous administration of IL-32α inhibited proliferation of the HTB-72 human melanoma cell line, but had little effect on other melanoma cell lines. Inhibition of proliferation in HTB-72 correlated with increased expression of p21 and p53. IL-32α administration also increased apoptosis in HTB-72. This finding correlated with increased expression of TRAILR1. CONCLUSIONS: The data presented suggest a direct effect of IL-32α on the growth of human melanoma and give some insight into the mechanisms which may in part govern this effect. J. Surg. Oncol. 2016;113:364-369. © 2016 Wiley Periodicals, Inc.


Subject(s)
Interleukins/pharmacology , Melanoma/drug therapy , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin-Dependent Kinase Inhibitor p21/biosynthesis , Humans , Immunohistochemistry , Melanoma/metabolism , Melanoma/pathology , Receptors, TNF-Related Apoptosis-Inducing Ligand/biosynthesis , Tumor Suppressor Protein p53/biosynthesis
9.
J Surg Oncol ; 111(8): 969-74, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25988864

ABSTRACT

BACKGROUND: IL-9 is a pleiotropic cytokine produced mainly by Th9 cells. IL-9 may have an anti-proliferative role in murine melanoma, however, its effect on human melanoma is unknown. METHODS: We examined the effects of IL-9 on proliferation and apoptosis in four human melanoma cell lines, HTB-65, HTB-72, CRL-11147, and SK-Mel-5. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis, as appropriate. RESULTS: We found that IL-9 decreased the percentage of colonies of HTB-72 and SK-Mel-5 cells but not that of HTB-65 or CRL-11147 cells. PCNA mRNA, PCNA+ cells, PCNA staining intensity, and the OD value of HTB-72 melanoma cells were consistently decreased in the present of IL-9. IL-9 also increased TUNEL+ cells and the relative caspase-3 activity in HTB-72 melanoma cells. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. The anti-proliferative effect of IL-9 on HTB-72 cells correlated with higher expression of anti-proliferative molecule p21. Its pro-apoptotic effect on HTB-72 cells correlated with higher expression of the pro-apoptotic molecule TRAIL. CONCLUSIONS: IL-9 inhibits melanoma HTB-72 cell growth by upregulation of p21 and TRAIL. Understanding the interactions between IL-9 and melanoma may help direct strategies for cytokine-based immunotherapy development.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p21/metabolism , Growth Inhibitors/metabolism , Interleukin-9/metabolism , Melanoma/drug therapy , TNF-Related Apoptosis-Inducing Ligand/metabolism , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Growth Inhibitors/pharmacology , Humans , Interleukin-9/pharmacology , Up-Regulation
10.
J Immunol ; 190(8): 3928-38, 2013 Apr 15.
Article in English | MEDLINE | ID: mdl-23509363

ABSTRACT

CD40 is expressed on cells of the immune system and in some tissues that are targets for autoimmune-mediated damage. It is not known if CD40 expression in target tissues plays a role in the pathology of autoimmune diseases. This study shows that agonistic anti-CD40 induces strong and sustained proliferation of thyroid epithelial cells (TECs), or thyrocytes, in IFN-γ(-/-) autoimmune-prone NOD and NOD.H-2h4 mice. TEC proliferation is accompanied by greatly increased expression of CD40 on TECs, development of fibrosis and hypothyroidism, and increased expression of proinflammatory molecules in thyroids. Bone marrow chimera experiments indicate that TEC expression of CD40 is required for anti-CD40-induced TEC proliferation, but lymphoid cells do not have to express CD40. TEC proliferation is reduced in wild-type mice given anti-CD40, presumably because they produce IFN-γ, which inhibits TEC proliferation. CD40 also increases on TECs during development of an autoimmune thyroid disease characterized by TEC hyperproliferation that develops spontaneously in IFN-γ(-/-) NOD.H-2h4 mice. TEC hyperproliferation development is accelerated in mice given agonistic anti-CD40. These studies provide new information regarding the role of target tissue expression of CD40 in development of autoimmunity and suggest that use of agonistic anti-CD40 for tumor therapy could result in autoimmune disease.


Subject(s)
Antibodies/physiology , Autoimmunity , CD40 Antigens/agonists , CD40 Antigens/immunology , Cell Proliferation , Epithelial Cells/immunology , Thyroid Gland/immunology , Thyroid Gland/metabolism , Animals , CD40 Antigens/biosynthesis , Epithelial Cells/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Inbred DBA , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Primary Cell Culture , Thyroid Gland/cytology
11.
Cytokine ; 70(2): 126-33, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25073578

ABSTRACT

Interleukin-35 (IL-35), an IL-12 cytokine family member, mediates the immune inhibitory function of regulatory T cells (Treg). We assayed the presence of IL-35 in paraffin-embedded human pancreas cancer (PCAN) and unexpectedly found IL-35 was expressed mainly by epithelial derived PCAN cells, but not by Treg. We further examined the expression and effect of exogenous IL-35 in human PCAN cell lines and found IL-35 promoted growth and inhibited apoptosis in PCAN cell lines. IL-35 induced proliferation correlated with an increase in cyclin B, cyclin D, cdk2, and cdk4 and a decrease in p27 expression, while inhibition of apoptosis was associated with an increase in Bcl-2 and a decrease in TRAILR1. We conclude IL-35 is produced by PCAN in vivo and promotes PCAN cell line growth in vitro. These results might indicate an important new role for IL-35 as an autocrine growth factor in PCAN growth.


Subject(s)
Apoptosis , Autocrine Communication , Interleukins/metabolism , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Antibodies, Neutralizing/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Autocrine Communication/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Humans , Interleukins/genetics , Neoplasm Proteins/metabolism , Pancreatic Neoplasms/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Interleukin/genetics , Receptors, Interleukin/metabolism
12.
Explor Target Antitumor Ther ; 5(5): 1135-1154, 2024.
Article in English | MEDLINE | ID: mdl-39351439

ABSTRACT

Bladder cancer is a leading cancer type in men. The complexity of treatment in late-stage bladder cancer after systemic spread through the lymphatic system highlights the importance of modulating disease-free progression as early as possible in cancer staging. With current therapies relying on previous standards, such as platinum-based chemotherapeutics and immunomodulation with Bacillus Calmette-Guerin, researchers, and clinicians are looking for targeted therapies to stop bladder cancer at its source early in progression. A new era of molecular therapies that target specific features upregulated in bladder cancer cell lines is surfacing, which may be able to provide clinicians and patients with better control of disease progression. Here, we discuss multiple emerging therapies including immune checkpoint inhibitors of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway, antibody-drug conjugates, modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) cell proliferation pathway, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor targeting. Together, these modern treatments provide potentially promising results for bladder cancer patients with the possibility of increasing remission and survival rates.

13.
Anticancer Res ; 44(5): 1807-1815, 2024 May.
Article in English | MEDLINE | ID: mdl-38677738

ABSTRACT

BACKGROUND/AIM: Recently developed vaccines for the SARS-CoV-2 virus utilize endogenous production of the virus' spike protein (SP), allowing the host to develop an immune response. As a result of the novelty of this virus and its vaccines, little is known overall about the potential effects of the SP on the pathogenesis of neoplasia, either from vaccination or from infection. This study was designed to investigate whether SARS-CoV-2 SP has any direct effect on SiHa cervical cancer cells. MATERIALS AND METHODS: The effects of SARS-CoV-2 SP on cervical cancer cell proliferation and apoptosis were investigated by using clonogenic cell survival assay, quick cell proliferation assay, and caspase-3 activity kits in a widely-used cervical cancer cell line, SiHa. RT-PCR and immunohistochemistry were also performed to determine the potential molecular mechanisms. RESULTS: The growth and proliferation of SiHa cancer cells were inhibited by SARS-CoV-2 SP. SARS-CoV-2 SP also induced apoptosis in SiHa cancer cells. The anti-proliferative effect of SARS-CoV-2 SP on SiHa cancer cells was associated with the up-regulation of the anti-proliferative molecule p53. The pro-apoptotic effect of SARS-CoV-2 SP on SiHa cells was associated with the up-regulation of the pro-apoptotic molecule TRAIL. CONCLUSION: SARS-CoV-2 SP inhibits the growth of cervical cancer via up-regulation of p53 and TRAIL. Further studies are needed to elaborate on the potential effects of the SARS-CoV-2 SP on other cancer cell lines and normal physiological cell lines for comparison.


Subject(s)
Apoptosis , Cell Proliferation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Female , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/genetics , Cell Line, Tumor , SARS-CoV-2/physiology , COVID-19/virology , COVID-19/metabolism , COVID-19/pathology , Tumor Suppressor Protein p53/metabolism , Caspase 3/metabolism
14.
Med Oncol ; 41(3): 65, 2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38281234

ABSTRACT

Cervical cancer is one of the most common types of female cancers worldwide. IL-29 is an interesting cytokine in the IFNλ family. Its role in the pathogenesis of neoplasia is complicated and has been studied in other cancers, such as lung cancer, gastric cancer, and colorectal cancer. IL-29 has been previously reported to promote the growth of pancreatic cancer. However, the direct role of IL-29 in cervical cancer has not been studied yet. This study was performed to investigate the direct effect on cervical cancer cell growth. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects of IL-29 on cell survival, proliferation, and apoptosis of a well-studied cervical cancer cell line, SiHa. We further investigated the potential molecular mechanisms by using RT-PCR and IHC. We found that the percentage of colonies of SiHa cells was decreased in the presence of IL-29. This was consistent with a decreased OD value of cancer cells. Furthermore, the relative caspase-3 activity in cancer cells increased in the presence of IL-29. The anti-proliferative effect of IL-29 on cancer cells correlated with increased expression of the anti-proliferative molecules p18 and p27. The pro-apoptotic effect of IL-29 on cancer cells correlated with increased expression of the pro-apoptotic molecule TRAILR1. IL-29 inhibits cervical cancer cell growth by inhibiting cell proliferation and promoting cell apoptosis. Thus, IL-29 might be a promising cytokine for immunotherapy of cervical cancer.


Subject(s)
Cytokines , Interferon Lambda , Interleukins , Uterine Cervical Neoplasms , Female , Humans , Apoptosis , Caspase 3 , Cell Line, Tumor , Cell Proliferation , Immunotherapy , Up-Regulation , Uterine Cervical Neoplasms/therapy
15.
Med Oncol ; 41(3): 67, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38286890

ABSTRACT

Ovarian cancer is a prominent cancer worldwide with a relatively low survival rate for women diagnosed. Many individuals are diagnosed in the late stage of the disease and are prescribed a wide variety of treatment options. Current treatment options are primarily a combination of surgery and chemotherapy as well as a new but promising treatment involving immunotherapy. Nevertheless, contemporary therapeutic modalities exhibit a discernible lag in advancement when compared with the strides achieved in recent years in the context of other malignancies. Moreover, many surgery and chemotherapy options have a high risk for recurrence due to the late-stage diagnosis. Therefore, there is a necessity to further treatment options. There have been many new advancements in the field of immunotherapy. Immunotherapy has been approved for 16 various types of cancers and has shown significant treatment potential in many other cancers as well. Researchers have also found many promising outlooks for immunotherapy as a treatment for ovarian cancer. This review summarizes many of the new advancements in immunotherapy treatment options and could potentially offer valuable insights to gynecologists aimed at enhancing the efficacy of their treatment approaches for patients diagnosed with ovarian cancer.


Subject(s)
Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/pathology , Immunotherapy
16.
Med Oncol ; 41(7): 181, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900341

ABSTRACT

As immunotherapy gains momentum as a promising approach for treating several types of cancer, IL-21 has emerged as the latest discovery within the γ chain cytokine family, known for its decisive effects on innate and adaptive immunity and immunopathology. Through the modulation of immune cells, IL-21 has demonstrated significant anti-tumor effects in preclinical studies. The potential of IL-21 in cancer treatment has been explored in phase I and II clinical trials, where it has been utilized both as monotherapy and in combination with other drug agents. Further investigation, alongside larger studies, is necessary before final evaluation and application of IL-21 as immunotherapy. This review aims to summarize these pre-clinical and clinical studies and to discuss the possible future directions of IL-21 immunotherapy development. Such a study may be helpful to accelerate the process of clinical application for IL21 immunotherapy.


Subject(s)
Immunotherapy , Interleukins , Neoplasms , Humans , Interleukins/therapeutic use , Interleukins/immunology , Immunotherapy/methods , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/drug therapy , Animals
17.
Med Oncol ; 41(10): 240, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39231878

ABSTRACT

Interleukin-22, discovered in the year of 2000, is a pleiotropic Th17 cytokine from the IL-10 family of cytokines. IL-22 signals through the type 2 cytokine receptor complex IL-22R and predominantly activates STAT3. This pathway leads to the transcription of several different types of genes, giving IL-22 context-specific functions ranging from inducing antimicrobial peptide expression to target cell proliferation. In recent years, it has been shown that IL-22 is involved in the pathogenesis of neoplasia in some cancers through its pro-proliferative and anti-apoptotic effects. This review highlights studies with recent discoveries and conclusions drawn on IL-22 and its involvement and function in various cancers. Such a study may be helpful to better understand the role of IL-22 in cancer so that new treatment could be developed targeting IL-22.


Subject(s)
Interleukin-22 , Interleukins , Neoplasms , Humans , Interleukins/metabolism , Neoplasms/metabolism , Neoplasms/immunology , Neoplasms/pathology , Animals , Signal Transduction , STAT3 Transcription Factor/metabolism , Receptors, Interleukin/metabolism , Receptors, Interleukin/genetics
18.
Curr Pharm Biotechnol ; 25(17): 2266-2277, 2024.
Article in English | MEDLINE | ID: mdl-38347797

ABSTRACT

BACKGROUND: Metagenomic next-generation sequencing (mNGS) demonstrates great promise as a diagnostic tool for determining the cause of pathogenic infections. The standard diagnostic procedures (SDP) include smears and cultures and are typically viewed as less sensitive and more time-consuming when compared to mNGS. There are concerns about the logistics and ease of transition from SDP to mNGS. mNGS lacks standardization of collection processes, databases, and sequencing. Additionally, there is the burden of training clinicians on interpreting mNGS results. OBJECTIVE: Until now, few studies have explored factors that could be used as early adoption candidates to ease the transition between SDP and mNGS. This study evaluated 123 patients who had received both SDP and mNGS and compared several variables across a diagnostic test evaluation. METHODS: The diagnostic test evaluation observed metrics such as sensitivity, specificity, positive and negative likelihood ratios (PLR, NLR), positive and negative predictive values (PPV, NPV), and accuracy. Factors included various sample sources such as bronchoalveolar lavage fluid (BALF), lung tissue, and cerebral spinal fluid (CSF). An additional factor observed was the patient's immune status. RESULTS: Pathogen detection was found to be significantly greater for mNGS for total patients, BALF sample source, CSF sample source, and non-immunocompromised patients (p<0.05). Pathogen detection was found to be insignificant for lung tissue sample sources and immunocompromised patients. Sensitivity, PLR, NLR, PPV, NPV, and accuracy appeared to be higher with mNGS for the total patients, BALF sample source, and non-immunocompromised patients when compared with SDP (p<0.05). CONCLUSION: With higher metrics in sensitivity, specificity, PLR, NLR, PPV, NPV, and accuracy for overall patients, mNGS may prove a better diagnostic tool than SDP. When addressing sample sources, mNGS for BALF-collected samples appeared to have higher scores than SDP for the same metrics. When patients were in a non-immunocompromised state, mNGS also demonstrated greater diagnostic benefits to BALF and overall patients compared to SDP. This study demonstrates that using BALF as a sample source and selecting non-immunocompromised patients may prove beneficial as early adoption factors for mNGS standard protocol. Such a study may pave the road for mNGS as a routine clinical method for determining the exact pathogenic etiology of lung infections.


Subject(s)
Bronchoalveolar Lavage Fluid , High-Throughput Nucleotide Sequencing , Metagenomics , Respiratory Tract Infections , Humans , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/standards , Metagenomics/methods , Metagenomics/standards , Respiratory Tract Infections/diagnosis , Bronchoalveolar Lavage Fluid/microbiology , Male , Middle Aged , Female , Aged , Adult , Sensitivity and Specificity
19.
Anticancer Res ; 44(7): 2775-2786, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38925849

ABSTRACT

BACKGROUND/AIM: Ovarian cancer (OVC) is a common, aggressive, and heterogeneous malignancy, with a widely variable prognosis. With the advances of modern immunology, mast cells (MCs) have been shown to play a significant role in the prognosis of some malignant tumors. However, the role of mast cells in the prognosis of OVC is unknown. MATERIALS AND METHODS: In this study, MC-associated prognostic genes (MRGs) were used to classify OVC from The Cancer Genome Atlas (TCGA)-OVC cohort. Genes were evaluated using univariate cox regression analysis. Twenty-nine prognostic gene signatures were identified using LASSO-COX analysis. COX regression models and principal component analysis (PCA) algorithms were used to construct MRG scores and individual MRGs patterns. External validation was performed in the TCGA-breast cancer (BRCA) and IMvigor210 cohorts. Immunity analysis based on MRGs was performed using CIBERSORT, and GSVA methods, and immunotherapy response was evaluated using the TIDE website. RESULTS: Using TCGA-OVC data, we established a model for constructing MRG scores based on the twenty-nine identified prognostic gene signatures using the PCA algorithm. MRG scores were found to be strongly correlated with immune cell infiltration and were excellent predictors of prognosis in patients with OVC. Low MRG scores were associated with better prognosis and better response to immunotherapy and chemotherapy. CONCLUSION: MC-related prognosis signature characterizes the immune landscape and predicts the prognosis of OVC. Understanding the correlation between MC-related gene signatures and immunotherapy and chemotherapy may improve the development of personalized clinical treatment strategies.


Subject(s)
Mast Cells , Ovarian Neoplasms , Humans , Female , Mast Cells/immunology , Mast Cells/pathology , Prognosis , Ovarian Neoplasms/immunology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/mortality , Biomarkers, Tumor/genetics , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Gene Expression Regulation, Neoplastic , Immunotherapy/methods , Gene Expression Profiling , Transcriptome
20.
Cell Metab ; 36(6): 1237-1251.e4, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38513648

ABSTRACT

Pancreatic ß cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as ß cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in ß cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in ß cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency. The role of Smad5 in regulating insulin processing and secretion attributes to its non-canonical function by regulating V-ATPase activity for granule acidification. Genetic mutation of Smad5 or administration of alkaline water to mirror cytosolic alkalization ameliorated glucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findings suggest that pHc is a direct nexus in linking environmental cues with insulin processing and secretion in ß cells.


Subject(s)
Cytosol , Insulin Secretion , Insulin-Secreting Cells , Insulin , Mice, Inbred C57BL , Animals , Insulin-Secreting Cells/metabolism , Hydrogen-Ion Concentration , Cytosol/metabolism , Mice , Insulin/metabolism , Male , Diet, High-Fat , Glucose Intolerance/metabolism , Glucose/metabolism , Humans
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