Can folate supplements be dangerous? - part 2

2010 ◽  
Vol 327 ◽  
pp. 1-5 ◽  

In a nutshellWhilst adequate folate is protective against cancer, there are theoretical grounds and some clinical evidence to suggest that, in people with existing pre-cancerous or cancer cells, folate supplements could stimulate their growth.However, more studies have failed to show this than have reported it, and so the hypothesis remains neither confirmed nor refuted. Until this matter is resolved, some caution is appropriate, particularly in those who may already have early stage tumour.

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3975
Author(s):  
Marco A. De Velasco ◽  
Yurie Kura ◽  
Naomi Ando ◽  
Noriko Sako ◽  
Eri Banno ◽  
...  

Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.


2021 ◽  
Vol 22 (14) ◽  
pp. 7356
Author(s):  
Justin D. Middleton ◽  
Jared Fehlman ◽  
Subhakeertana Sivakumar ◽  
Daniel G. Stover ◽  
Tsonwin Hai

Previously, we showed that chemotherapy paradoxically exacerbated cancer cell colonization at the secondary site in a manner dependent on Atf3, a stress-inducible gene, in the non-cancer host cells. Here, we present evidence that this phenotype is established at an early stage of colonization within days of cancer cell arrival. Using mouse breast cancer models, we showed that, in the wild-type (WT) lung, cyclophosphamide (CTX) increased the ability of the lung to retain cancer cells in the vascular bed. Although CTX did not change the WT lung to affect cancer cell extravasation or proliferation, it changed the lung macrophage to be pro-cancer, protecting cancer cells from death. This, combined with the initial increase in cell retention, resulted in higher lung colonization in CTX-treated than control-treated mice. In the Atf3 knockout (KO) lung, CTX also increased the ability of lung to retain cancer cells. However, the CTX-treated KO macrophage was highly cytotoxic to cancer cells, resulting in no increase in lung colonization—despite the initial increase in cell retention. In summary, the status of Atf3 dictates the dichotomous activity of macrophage: pro-cancer for CTX-treated WT macrophage but anti-cancer for the KO counterpart. This dichotomy provides a mechanistic explanation for CTX to exacerbate lung colonization in the WT but not Atf3 KO lung.


2015 ◽  
Vol 7 (4) ◽  
Author(s):  
Jyoti Verma ◽  
Sumit Lal ◽  
Cornelis J.F. Van Noorden

AbstractTheranostics are a multifunctional approach using nanoparticles for combined diagnostic and therapeutic purposes. The hybrid nanoparticles that are applied for these purposes are composed of an inorganic core and an organic shell. The inorganic core acts as a contrast enhancer and the organic shell acts as a drug releaser. Hybrid nanoparticles can be conjugated with targeting moieties and systematically administered to patients to direct the nanoparticles to specific cells such as cancer cells. Theranostics have the potential to significantly improve early stage cancer diagnostics and patient survival. This review discusses preclinical and clinical advances in applications of inorganic nanoparticles for the theranostics of cancer.


Author(s):  
Qing Ye ◽  
Yuanfei Peng ◽  
Feng Huang ◽  
Jinhu Chen ◽  
Yangmei Xu ◽  
...  

Background: In previous studies, we provided evidence suggesting the involvement of γ-synuclein in growth, invasion, and metastasis of colon cancer cells in vitro and in vivo. Among γ-synuclein downstream genes, the microtubule-associated protein 1 light chain 3 (LC3), an autophagy gene, was screened by gene expression profile chip analysis. Objective: We planned to investigate the functional effects of γ-synuclein on autophagy induced by ER stress in colon cancer cells. Methods: We investigated the functional effects of γ-synuclein on autophagy and apoptosis induced by Thapsigargin (TG), ER stressinducing agent, in colon cancer cell lines using immunofluorescence staining, RT-PCR, western blot, CCK8 test, flow cytometry analysis, and transmission electron microscopy. To further determine how γ-synuclein regulated autophagy and apoptosis, PD98059 (ERK inhibitor), SP600125 (ERK inhibitor), anisomycin (JNK activator), and c-Jun siRNA were used respectively in γ-synuclein siRNA transfected HCT116 cells. Then, autophagy proteins, apoptosis proteins, and pathway proteins were detected by western blot analysis. The expression of autophagy genes was assessed by RT-PCR. Results: Our data showed that ER stress-induced colon cancer cells autophagy mainly in the early stage (0-24h) and apoptosis mainly in the late stage (24-48h). ER stress up-regulated γ-synuclein gene and protein expression in colon cancer cells, accompanied by autophagy. γ-synuclein protected HCT116 cells by enhancing autophagy in the early stage (0-24h) through activation of ERK and JNK pathway and inhibiting apoptosis in the late stage (24-48h) through inhibition of the JNK pathway. γ-synuclein could promote autophagy via the JNK pathway activation of ATG genes, LC3, Beclin 1, and ATG7. γ-synuclein may play a role in the transition between autophagy and apoptosis in our model. Conclusion: Overall, we provided the first experimental evidence to show that γ-synuclein may play an important role in autophagy that protects colon cancer cells from ER stress. Therefore, our data suggest a new molecular mechanism for γ-synuclein-mediated CRC progression.


Cancer Cell ◽  
2015 ◽  
Vol 27 (2) ◽  
pp. 193-210 ◽  
Author(s):  
Hai Wang ◽  
Cuijuan Yu ◽  
Xia Gao ◽  
Thomas Welte ◽  
Aaron M. Muscarella ◽  
...  

Author(s):  
Kodieswari A.

Cancer disease is the second largest disease in the world with high death mortality. Cancer is an abnormal growth of a normal cell. There are more than 100 types of cancer like blood cancer, brain cancer, small intestine cancer, lung cancer, liver cancer, etc. The type of cancer can be classified by the type of cell which is initially affected. When cancer grows it does not show any symptom. The symptom will appear when the cancer cell grows in mass and the symptom of cancer depends on the type of cancer. The cause of cancers is environmental pollutants, food habits, inherited genetics, tobacco, stress, etc., but in practice, it is not possible to prove the cause of cancer since various cancers do not have specific fingerprints. After the heart attack, cancer is a second killer disease in India. The death mortality is high in cancer because in most of the cases it is identified at the final stage which causes more death. According to ICMR, among 1.27 billion Indian populations, the incidence of cancer is 70-90 per 100,000 populations and 70% of cancer is identified in the last stage accounting for high morality. There are many types of treatment to treat cancer and they are surgery, radiation therapy, chemotherapy, targeted therapy, hormone therapy, stem cell transplant, etc. All cancer treatments will have side effects and the treatments will help only if the cancer cells are identified at the early stage. So time factor is important in diagnosing of cancer cells; hence, early detection of cancer will reduce the mortality rate. This chapter proposed the early detection of cancer cells using image processing techniques by the structure of circulating tumor cell. Early detection of cancer cells is very difficult because the concentration of cancer cells are extremely small and about one million malignant cell is encountered per billion of healthy cells. The circulating tumor cells, CTC, are shed into the bloodstream as a tumor grows, and it is believed these cells initiate the spread of cancer. CTC are rare, existing as only a few per one billion blood cells, and a highly efficient technology like chip-based biosensor platforms is required to capture the CTC, which in turn helps to detect cancer cell at an early stage before spreading. In proposed method, the circulating tumor cell has used a marker to detect cancer at early stage.


2018 ◽  
Vol 5 (1) ◽  
pp. 24-30
Author(s):  
Fatema Tuj Johora ◽  
Mehdi Hassan Jony ◽  
Md Shakhawat Hossain ◽  
Humayun Kabir Rana

Lung cancer is one of the most dangerous diseases and prediction of it, is the most challenging problem nowadays. Most of the cancer cells are overlapped with each other. It is hard to detect the cells but also essential to identify the presence of cancer cells in the early stage. Early detection of lung cancer may reduce the death rate. In this study, we used the Grey Level Co-occurrence Matrix (GLCM) to extract the feature of cancer affected lung image and then Support Vector Machine (SVM) has been used to detect normal and abnormal lung cells after implementing the features. Our experimental evaluation using MATLAB demonstrates the efficient performance of the proposed system and in the result. GUB JOURNAL OF SCIENCE AND ENGINEERING, Vol 5(1), Dec 2018 P 24-30


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Manuel Scimeca ◽  
Nicoletta Urbano ◽  
Bonfiglio Rita ◽  
Sarah Natalia Mapelli ◽  
Carlo Vittorio Catapano ◽  
...  

The main aim of this study was to investigate the putative association among the presence of prostate cancer cells, defined as prostate osteoblast-like cells (POLCs), and showing the expression of typical morphological and molecular characteristics of osteoblasts, the development of bone metastasis within 5 years of diagnosis, and the uptake of 18F-choline evaluated by PET/CT analysis. To this end, prostate biopsies (n= 110) were collected comprising 44 benign lesions and 66 malignant lesions. Malignant lesions were further subdivided into two groups: biopsies from patients that had clinical evidence of bone metastasis (BM+,n= 23) and biopsies from patients that did not have clinical evidence of bone metastasis within 5 years (BM−,n= 43). Paraffin serial sections were obtained from each specimen to perform histological classifications and immunohistochemical (IHC) analysis. Small fragments of tissue were used to perform ultrastructural and microanalytical investigations. IHC demonstrated the expression of markers of epithelial-to-mesenchymal transition (VIM), bone mineralization, and osteoblastic differentiation (BMP-2, PTX-3, RUNX2, RANKL, and VDR) in prostate lesions characterized by the presence of calcium-phosphate microcalcifications and high metastatic potential. Ultrastructural studies revealed the presence of prostate cancer cells with osteoblast phenotype close to microcalcifications. Noteworthy, PET/CT analysis showed higher uptake of 18F-choline in BM+ lesions with high positivity (≥300/500 cells) for RUNX2 and/or RANKL immunostaining. Although these data require further investigations about the molecular mechanisms of POLCs generation and role in bone metastasis, our study can open new and interesting prospective in the management of prostate cancer patients. The presence of POLCs along with prostate microcalcifications may become negative prognostic markers of the occurrence of bone metastases.


2019 ◽  
Vol 110 (6) ◽  
pp. 1842-1852 ◽  
Author(s):  
Yu Akazawa ◽  
Daisuke Nobuoka ◽  
Mari Takahashi ◽  
Toshiaki Yoshikawa ◽  
Manami Shimomura ◽  
...  

2012 ◽  
Vol 27 (4) ◽  
pp. 344-352 ◽  
Author(s):  
Huan-Chieh Cho ◽  
Chien- Huang Liao ◽  
Alice L Yu ◽  
John Yu

Most cancers are detected when patients present with symptoms, and at that point the disease is usually quite advanced and often not curable. Therefore, new biomarkers are needed for detection and therapy. The recent success of using monoclonal antibodies against nonprotein gangliosides for the treatment of high-risk neuroblastoma provides an incentive to search for new glycan-targeted immunotherapies for cancer using markers found through glycomic analysis as targets. Since more than 85% of cell surface components are glycosylated, glycomic analysis is useful to probe systematically the cancer cell surface, in search for novel glycoproteins and glycolipids. Furthermore, cancer cells tend to dedifferentiate and express many oncofetoproteins, since human embryonic stem cells (ESCs) are derived from epiblast of embryo, representing the early stage of normal embryonic development before gastrulation. Unique ESC surface markers are likely to be found in cancer cells, but not in normal mature tissues. Moreover, stem cells and cancer cells share several common features in related regulatory mechanisms and signaling pathways. Thus, identification of the cancer stem cells in cancer and definition of the glycoproteomic changes that accompany their transformation are important for the development of strategies for early detection and treatment of cancer.


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