• Genomics & Informatics
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• v.21 no.1
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• pp.11.1-11.5
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• 2023

Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564 (with an average of 30,591) compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2827-2832
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• 2015

Oxidative stress is associated with colon carcinogenesis including aberrant crypt foci (ACF) formation and it plays an important role in pathophysiological changes in cancer cells. The aims of this study were to investigate the effects of dietary unpolished Thai rice (UTR) on ACF formation and dysplastic progression in azoxymethane (AOM)-treated rats. Anti-cancer efficacy of UTR regarding apoptotic induction and oxidative redox status in human colon cancer (CaCo-2) cells was also investigated. Rats given 20% and 70% of UTR in the diet showed significantly and dose-dependently decreased total number of ACF. UTR treatment also was strongly associated with the low percentage of dysplastic progression and mucin depletion. In addition, we found that UTR significantly induced cancer cell apoptosis, increased cellular oxidants, and decreased the level of GSH/GSSG ratio in CaCo-2 cells. Our study suggests that UTR supplementation may be a useful strategy for CRC prevention with the inhibition of precancerous progression, with induction of cancer cell apoptosis through redox alteration.

• Genomics & Informatics
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• v.12 no.4
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• pp.156-164
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• 2014

Cancer is the most dreaded disease in human and also major health problem worldwide. Despite its high occurrence, the exact molecular mechanisms of the development and progression are not fully understood. The existing cancer therapy based on allopathic medicine is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a non-toxic and effective mode of treatment is needed to control cancer development and progression. Some medicinal plants offer a safe, effective and affordable remedy to control the cancer progression. Nimbolide, a limnoid derived from the neem (Azadirachta indica) leaves and flowers of neem, is widely used in traditional medical practices for treating various human diseases. Nimbolide exhibits several pharmacological effects among which its anticancer activity is the most promising. The previous studies carried out over the decades have shown that nimbolide inhibits cell proliferation and metastasis of cancer cells. This review highlights the current knowledge on the molecular targets that contribute to the observed anticancer activity of nimbolide related to induction of apoptosis and cell cycle arrest; and inhibition of signaling pathways related to cancer progression.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.213-220
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• 2022

Although there have been advances in cancer therapy and surgical improvement, lung cancer has the lowest survival rate (19%) at all stages. This is because most patients are diagnosed with concurrent metastasis, which occurs due to numerous related reasons. Especially, lung cancer is one of the most common and malignant cancers in the world. Although there are advanced therapeutic strategies, lung cancer remains one of the main causes of cancer death. Recent work has proposed that epithelial-mesenchymal transition (EMT) is the main cause of metastasis in most cases of human cancers including lung cancer. EMT involves the conversion of epithelial cells, wherein the cells lose their epithelial abilities and become mesenchymal cells involved in embryonic development, such as gastrulation and neural crest formation. In addition, recent research has indicated that EMT contributes to altering the cancer cells into cancer stem cells (CSCs). Although EMT is important in the developmental stages, this process also activates lung cancer progression, including complicated and diverse signaling pathways. Despite the numerous investigations on signaling pathways involved in the progression of lung cancer, this malignancy is considered critical for treatment. EMT in lung cancer involves many transcription factors and inducers, for example, Snail, TWIST, and ZEB are the master regulators of EMT. EMT-related factors and signaling pathways are involved in the progression of lung cancer, proposing new approaches to lung cancer therapy. In the current review, we highlight the signaling pathways implicated in lung cancer and elucidate the correlation of these pathways, indicating new insights to treat lung cancer and other malignancies.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3605-3616
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• 2015

Cancer is basically a class of disorder marked by uncontrolled proliferation of cells which have the potential to interfere with different systems of body like digestive, central nervous and circulatory systems by releasing hormones. Tumors that reside only in a specified location and show restricted growth are commonly characterized as benign tumors. When tumor cells grow and effectively spread to other body parts and potentially invade and damage healthy tissues they show various degrees of malignancy. Cancer may be caused by different factors like gene mutations, carcinogens and some medical factors that harm the immune system of the body. Symptoms of cancer are relatively varied and classified according to location, progression pattern and size of tumors as well. Different diagnostic tests are used for evaluation that depends on the type of cancer. Cancer management and chemo protocols also depend on the progression and site where it develops. Cancers like breast, lung, liver, colorectal, prostate, head and neck carcinoma are most commonly diagnosed in Pakistan. This review briefly describes the three most common cancers prevailing in Pakistan and their management evaluation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10837-10840
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• 2015

To assess survival outcomes in a retrospective study, recurrent epithelial ovarian cancer patients were divided into three groups according to the platinum free interval as follows: platinum refractory that included the patients with tumor progression during treatment; platinum resistant and platinum sensitive that included the patients with tumor progression less than or more than six months, respectively. Clinical data for tumor progression in epithelial ovarian cancer patients treated at Chiang Mai University Hospital between January, 2006 and December, 2010 were reviewed. Thirty-nine patients were in the platinum refractory group while 27 were in the platinum resistant group and 75 in the platinum sensitive group. The mean age, the parity, the administration of neoadjuvant chemotherapy and the serous type did not significantly different across groups while the mean total number of chemotherapy regimens, the early stage patients, the patients with complete surgery and the surviving patients were significant more frequent in the platinum sensitive group. Regarding subsequent treatment after tumor recurrence, 87.2% underwent chemotherapy. With the median follow up time at 29 months, the median overall survival rates were 20 months, 14 months and 42 months in platinum refractory, platinum resistant and platinum sensitive groups, respectively (p<0.001). In addition, when the platinum sensitive patients developed the next episode of tumor progression, the median progression free interval time was only three to four months. In conclusion, the outcomes for platinum refractory the and platinum resistant groups was poorer than the platinum sensitive group. However, subsequent progression in the platinum sensitive group was also associated with a poor outcome.

• Journal of Yeungnam Medical Science
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• v.36 no.2
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• pp.159-162
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• 2019

The most cases with orbital metastases have been reported in patients with a prior established diagnosis of cancer and widespread systemic involvement. However, ocular symptoms can be developed as an initial presentation of cancer in patients without cancer history. We report a case of rapid progression from trochlear nerve palsy to orbital apex syndrome as an initial presentation of advanced gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10401-10405
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• 2015

Background: Molecular prognostic markers have been under investigation for the last decade and no validated marker to date has been proven to be used in daily clinical practice for urinary bladder cancers. The aim of the present study is to evaluate the significance of HYAL-1 expression in prediction of recurrence and progression in pT1 urothelial carcinomas. Materials and Methods: Eighty-nine urothelial carcinoma cases staged as T1 according to 2004 WHO classification were studied. Representative sections from every case were stained immunohistochemically for HYAL-1 and scored between 0 and +3, according to staining density, and graded as low and high for the scores 0-1 and 2-3, respectively. Results: Of the 89 pT1 bladder cancer patients, HYAL-1 expression was high in 92.1% (82 patients; 72 patients +3 and 10 patients +2) and low in 7.9% (only 7 patients; 6 patients +1 and 1 patient 0) of the cases. Of the 89 patients, 38 (42.7%) had recurrence and 22 (24.7%) showed progression. HYAL-1 staining did not show significant characteristics for tumor grade, accompanying CIS, multiplicity, tumor size, age and sex. HYAL-1 expression did not have any prognostic value in estimating recurrence or progression. Conclusions: HYAL-1 expression was found to be high, but did not have any prognostic importance in T1 bladder urothelial carcinomas.

• Korean Journal of Clinical Pharmacy
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• v.14 no.1
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• pp.1-10
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• 2004

Studies of oxaliplatin, 5-fluorouracil and leucovorin in pretreated metastatic colorectal cancer showed that oxaliplatin dose intensity is important prognostic factor for objective response rates and progression-free-survival (PFS). To evaluate response rates, PFS and toxicity according to oxaliplatin dose intensity, we retrospectively analyzed data from patients with metastatic colorectal cancer received oxaliplatin,5-fluorouracil, leucovorin regimens. Sixty-three patients were reviewed in this study, 42 patients received low dose intensity oxaliplatin (LDI: $\leq85\;mg/m^2/2wks$) and 21 patients high dose intensity oxaliplatin (HDI: $>85\;mg/m^2/2wks$). Objective responses occurred in 10 $(47.7\%)$ HDI patients and 9 $(21.4\%)$ LDI patients (p = 0.014). Median PFS was 24.7 weeks in HDI group, with $45.1\%$ of HDI patients progression free at 6 months, and 20.5 weeks in LDI group, with $33.5\%$ of LDI patients progression free at 6 months (p = 0.344). Increased oxaliplatin dose intensity was not associated with neutropenia, thrombocytopenia, neuropathy, nausea and vomiting. This study showed that oxaliplatin dose intensification significantly improves objective response rate in pretreated metastatic colorectal cancer without increasing severe toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1001-1006
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• 2015

Background: With development and application of new and effective anti-cancer drugs, the median survival post-progression (SPP) is often prolonged, and the role of the median SPP on surrogacy performance should be considered. To evaluate the impact of the median SPP on the correlation between progression-free survival (PFS) and overall survival (OS), we performed simulations for treatment of four types of cancer, advanced gastric cancer (AGC), metastatic colorectal cancer (MCC), glioblastoma (GBM), and advanced non-small-cell lung cancer (ANSCLC). Materials and Methods: The effects of the median SPP on the statistical properties of OS and the correlation between PFS and OS were assessed. Further, comparisons were made between the surrogacy performance based on real data from meta-analyses and simulation results with similar scenarios. Results: The probability of a significant gain in OS and HR for OS was decreased by an increase of the SPP/OS ratio or by a decrease of observed treatment benefit for PFS. Similarly, for each of the four types of cancer, the correlation between PFS and OS was reduced as the median SPP increased from 2 to 12 months. Except for ANSCLC, for which the median SPP was equal to the true value, the simulated correlation between PFS and OS was consistent with the values derived from meta-analyses for the other three kinds of cancer. Further, for these three types of cancer, when the median SPP was controlled at a designated level (i.e., < 4 months for AGC, < 12 months for MCC, and <6 months for GBM), the correlation between PFS and OS was strong; and the power of OS reached 34.9% at the minimum. Conclusions: PFS is an acceptable surrogate endpoint for OS under the condition of controlling SPPs for AGC, MCC, and GBM at their limit levels; a similar conclusion cannot be made for ANSCLC.