Journal of Cancer Science and Clinical Therapeutics

Journal Information
EISSN : 2637-5079
Current Publisher: Fortune Journals (10.26502)
Total articles ≅ 103

Latest articles in this journal

Jose Atencia Goñi, Rogelio García-Centeno, María Picallo Pérez, Pascual Elvira Ruiz, Laura González Fernández, Olga González Albarrán
Journal of Cancer Science and Clinical Therapeutics, Volume 5, pp 114-123; doi:10.26502/jcsct.5079105

Tyroid-stimulatin hormone (TSH) - producing pituitary adenomas known as thyrotropinomas or TSHomas account for a small percentage of pituitary tumors [1]. Approximately 30% of them co-secrete growth hormone (GH), Prolactin, or αGSU of TSH [2]. We introduce a patient with a 12 years follow-up at our center with medical treatment by long-acting somatostatin analogues (SSA) due to rejected surgery. Along the treatment there is a scape with a secondary production of GH without image changes at the MRIs. We suggest a progressively acquired resistance to the medical treatment.
Sharon Amir, Snir Dekalo, Joseph Friedman, Nicola J Mabjeesh
Journal of Cancer Science and Clinical Therapeutics, Volume 5, pp 94-105; doi:10.26502/jcsct.5079103

Background: Increased levels of hypoxia-inducible factor 1α (HIF-1α) are related to poor prognosis and treatment failure in prostate cancer. The effect of extremely low frequency magnetic fields (ELF-MF), generally emitted from electronic devices on HIF-1α in cancer cells and, specifically, in prostate cancer is not well described. This study aimed to investigate the effects of ELF-MF on HIF- 1α protein expression and HIF-1 transcriptional activity in prostate cancer cells. Methods: Prostate cancer cells were irradiated with ELF-MF by means of a frequency generator at 875 MHz with an intensity of 0.07 mW/cm2 at various time periods and with an exposure system housed in a tissue culture incubator. The expression of HIF-1α protein and HIF-1 transcriptional activity at the different conditions were evaluated. Results: HIF-1α expression in different prostate cancer cells was higher after one hour of exposure to ELF-MF. All exposed cells also demonstrated a significant 50% increase in HIF-1 transcriptional activity as measured by an HRE-dependent reporter gene assay after ELF-MF irradiation. Cells exposed to ELF-MF exhibited 3-fold longer HIF-1α half-life compared to non-exposed control cells, while its mRNA levels were not affected. Immunofluorescence staining confirmed nuclear HIF-1α accumulation following exposure to ELF-MF. Cell proliferation was increased following ELF-MF exposure and significantly reduced when HIF-1α was silenced even after exposure to ELF-MF. Conclusions: Exposure of prostate cancer cells to ELF-MF increases HIF-1α protein stability and upregulates HIF-1 transcriptional activity. These findings provide new insights into the effects of ELF-MF on the hypoxic pathway which are important for guiding future implications.
Bhuiyan Mzr, Hasan T, Rasheed Mo, Sharmin S, Razib Sfa
Journal of Cancer Science and Clinical Therapeutics, Volume 5, pp 106-113; doi:10.26502/jcsct.5079104

Background: The present study was aimed at describing a multicentre clinical experience in the treatment of Inoperable carcinoma pyrifom fossa. Carcinoma pyriform fossa is the most frequent cancer arising from the hypopharynx, is rarely diagnosed in its early stage and still a leading cause of mortality and morbidity in developing countries. Despite improvement in overall survival for pyriform fossa cancer, the locally advanced cancer remains essentially incurable. Methods: This prospective observational study was carried out to compare the effects of concurrent chemoradiation and radiotherapy alone in locally advanced carninoma pyriform fossa cancer. The main objectives of this study are to assess the response and early toxicities in both concurrent chemoradiation and radiotherapy alone. Results: A total number of 90 patients, 45 in each arm having advanced pyriform fossa cancer were included in the study. Highest percentage of the patients was habituated with smoking, betal nut chewing and tobacco leaf user. The most common presenting symptoms were cervical lymphadenopathy, sore throat and hoarseness of voice. Overall response of patients treated with concurrent chemoradiation was better than in comparison to only radiotherapy. As only a new treatment of locally advanced carcinoma of pyriform fossa concurrent chemoradiation (group-A) represents better symptom improvement, more toxicities and better tumor responses than radiotherapy alone (group-B) regimen. Conclusion: In the treatment of locally advanced carcinoma pyriform fossa, concurrent chemoradiation with paclitaxel (40mg/m2I/V) weekly, represents better symptom improvement, tumor responses with manageable toxicities than radiotherapy alone.
Paula Díaz, Alejandra Román, Gonzalo Carrasco-Aviño, Andrés Rodríguez, Alejandro H Corvalán, Sergio Lavandero, Andrew Fg Quest
Journal of Cancer Science and Clinical Therapeutics, Volume 5, pp 63-82; doi:10.26502/jcsct.50790101

Infection by Helicobacter pylori (Hp) is the main risk factor associated with the development and progression of precancerous lesions to gastric cancer. Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is activated by endoplasmic reticulum (ER) stress, and ER stress-induced apoptotic cell death has been associated with Hp infection. Survivin, an inhibitor of apoptosis, is downregulated in the mucosa of Hp infected subjects and loss of survivin in gastric cells correlates with reduced viability. Here, we determined whether Hp-induced changes in PERK contribute to the loss of survivin, previously associated with the genesis of gastric cancer precancerous lesions. Our results show that PERK is activated in the early stages of Hp infection in the human gastric mucosa affected by gastritis and PERK activation coincided with reduced survivin levels compared with Hp-negative gastritis. Upon Hp infection in vitro, PERK silencing restored survivin abundance and its activity increased survivin loss, in parallel with a partial downstream activation of the α- subunit of eukaryotic initiation factor-2 (eIF2α). Our results suggest a novel mechanism by which Hp-stimulated PERK reduces gastric cell viability/proliferation by downregulating survivin and is likely to favour the genesis of gastric cancer precancerous lesions.
Jason Ricciuti, Devi Jaychandran, Peter Frederick
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 304-313; doi:10.26502/jcsct.5079073

Intravenous Lipoleiomyomatosis Mimicking Malignant Degeneration of Leiomyoma. PubMed, SCI, Scopus, ESCI, PMC indexed
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 365-368; doi:10.26502/jcsct.5079078

Neuropilin-1, A Rising Star in Cancer Immunotherapy. PubMed, SCI, Scopus, ESCI, PMC indexed
Minakshi Mann, Shyam S Chauhan, Neerja Bhatla, Sunesh Kumar, Sameer Bakhshi, Ritu Gupta, Sandeep Mathur, Lalit Kumar
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 266-282; doi:10.26502/jcsct.5079071

Development of resistance to cisplatin (CDDP) is a major bottleneck to treat cancer with CDDP, including cervical cancer (CC). We have recently shown that PARP-1 inhibition targets β-catenin signaling and enhance CDDP sensitivity in cervical cancer. This indicates that β-catenin itself could serve as an absolute target to potentiate CDDP cytotoxicity. So, we determined the effect of β-catenin inhibition using JW74 either alone or in combination CDDP using CC cell lines on cell vaibility, apoptosis, cell cycle progression, proliferation, invasion and metastasis, clonogenecity. However, unexpectedly β-catenin inhibitor JW74 failed to significantly enhance CDDP- cytotoxicity in both the cell lines. Since PARP-1 inhibitors inhibited β-catenin also, as determined through our previous work, so, we evaluated effect of JW74 mediated β-catenin inhibition on PARP-1 expression level inside cell. Intriguingly, we found that JW74 treatment enhanced PARP-1 expression as determined through western blotting. Increased PARP-1 serves responsible for CDDP resistance, thereby this seems stands responsible limiting our hypothesis. Further to confirm this, PARP-1 inhibitor PJ34 was added to a combination of JW74+CDDP and this significantly reduced cell survival and proliferation, enhanced cell death and decreased invasion and migration, hence enhanced CDDP sensitivity in CC cells. PJ34 with CDDP served as a better combination to increase caspase-3/7 cleavage, hence apoptosis, than combination of JW74 and CDDP; with PJ34 itself being less toxic to cells. Also PARP-1 expression was determined in human cervical cancer tissue sample at base level and compared to normal tissue sample. PARP-1 expression was significantly enhanced in human cervix cancer tumor samples. In summary, β-catenin inhibition increases PARP-1 expression, thereby, limits ability of β -catenin inhibitors to enhance CDDP cytotoxicity. Enhanced PARP-1 expression in cervix cancer tissue samples shows feasibility of using PARP-1 inhibitors in cervical cancer treatment.
Johanna Samulin Erdem, Øivind Skare, Marte Petersen-Øverleir, Heidi Ødegaard Notø, Jenny-Anne S. Lie, Kristina Kjærheim, Edyta Reszka, Beata Pepnolska, Shanbeh Zienolddiny
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 245-255; doi:10.26502/jcsct.5079069

Shift work, particularly, night work has been classified as a probable carcinogen to humans based on the increased risk observed in epidemiological studies for some cancer types, including female breast cancer. The underlying molecular mechanisms are not well established, but may involve aberrant epigenetic modifications. Here, effects of changes in methylation status of 5-methyl cytosine in melatonin and female hormone receptor genes were investigated as possible mechanisms for increased breast cancer risk in female night shift workers. Methylation in promoter regions of the MTNR1A, MTNR1B, PGR, ESR1 and ESR2 genes was analyzed by pyrosequencing in a nested case-control study of female nurses, including 354 breast cancer cases and 356 healthy controls. The effects of methylation as well as the combined effects of methylation and shift work on breast cancer risk were assessed. We demonstrate that increased methylation of the MTNR1A promoter is associated with increased risk of breast cancer (OR=1.13, 95% CI: 1.02 -1.24, P=0.019). No association between promoter methylation levels and breast cancer risk was observed for the other receptor genes investigated. Furthermore, MTNR1A methylation levels were not affected by shift work. Altogether, our data suggest that epigenetic regulation of MTNR1A may contribute to breast cancer.
Sharon M. Landers, Angela D. Bhalla, Xiaoyan Ma, Kristelle Lusby, Davis Ingram, Ghadah Al Sannaa, Wei-Lien Wang, Alexander J. Lazar,
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 511-525; doi:10.26502/jcsct.5079091

Dysregulation of the receptor tyrosine kinase AXL is known to promote cancer cell growth and survival in many sarcomas, including the rare subtype, malignant peripheral nerve sheath tumors (MPNST). MPNSTs are largely chemoresistant and carry a poor prognosis. AXL is an attractive potential therapeutic target, as it is aberrantly expressed, and its activation may be an early event in MPNST. However, the effect of AXL inhibition on MPNST development and progression is not known. Here, we investigated the role of AXL in MPNST development and the effects of AXL and MEK1/2 co-inhibition on MPNSTs. We used western blotting to examine AXL expression and activation in MPNST cell lines. We analyzed the effects of exogenous growth arrest-specific 6 (GAS6) expression on downstream signaling and the proliferation, migration, and invasion of MPNST cells. The effect of AXL knockdown with or without mitogen-activated protein kinase (MAPK) inhibition on downstream signal transduction and tumorigenesis was also examined in vivo and in vitro. We found that AXL knockdown increased MAPK pathway signaling. This compensation, in turn, abrogated the antitumorigenic effects linked to AXL knockdown in vivo. AXL knockdown, combined with pharmacological MEK inhibition, reduced the proliferation and increased the apoptosis of MPNST cells both in vitro and in vivo. The pharmacological co-inhibition of AXL and MEK1/2 reduced MPNST volumes. Together these findings suggest that AXL inhibition enhances the sensitivity of MPNST to other small molecule inhibitors. We conclude that combination therapy with AXL inhibitor may be a therapeutic option for MPNST.
Anne Merete Aaland Tryggestad, Iris Bigalke, Wolfgang Lilleby, Karol Axcrona, Turid Kirsti Hønnåshagen, Lisbeth Johanne Skoge, Stein Sæbøe-Larssen, Guri Solum, Richard Willfred Olaussen, Dag Josefsen, et al.
Journal of Cancer Science and Clinical Therapeutics, Volume 4, pp 393-407; doi:10.26502/jcsct.5079081

Objective: To investigate the clinical effects of novel therapeutic dendritic cell vaccines targeting the universal tumour antigens human telomerase reverse transcriptase and Survivin in a small exploratory group of four patients with high-risk prostate cancer who had progression after secondary therapy. In contrast to previous dendritic cell vaccine studies, we explored application of intradermal dendritic cell vaccines every month over longer periods of time to boost and maintain potential immune responses. Methods: Dendritic cell vaccines were given in combination with androgen deprivation therapy, with and without radiotherapy and chemotherapy, until tumour progression. PSA levels were followed throughout the whole treatment period. Immune responses were assessed investigating antigen specific CD4 and CD8 T cell responses at chosen time points. Results: Two patients remained in clinical remission at 113 and 72 months after start of dendritic cell vaccination. Time to progression for these two patients after secondary therapy, prior to dendritic cell vaccination was 3 and 7 months, respectively. A third patient obtained a stable clinical disease for 95 months with DC vaccines, androgen deprivation therapy and radiotherapy, with time to progression of only 14 months after secondary therapy but before start of vaccination. These patients mounted specific immune responses during dendritic cell vaccination as detected at several time points during treatment. Conclusion: These results suggest that patients with low tumour burden may benefit significantly from continuous personalized dendritic cell vaccination when combined with additional therapies. Importantly, no vaccine-related toxicity was observed despite application of substantial numbers of dendritic cells over extended periods of time. These exploratory cases provide valuable information regarding further studies of dendritic cell vaccination in larger numbers of high-risk prostate cancer patients for whom prolongation of time to progression is of high medical relevance.
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