• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5095-5099
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• 2013

Background: The overall incidence of breast cancer in South Asian countries, including Nepal, is low compared to Western countries. However, the incidence of breast cancer among young women is relatively high. Breast cancer in such cases is characterized by a relatively unfavorable prognosis and unusual pathological features. The aim of this study was to investigate clinico-pathological and biological characteristics in younger breast cancer patients (<40 years) and compare these with their older counterparts. Materials and Methods: Nine hundred and forty four consecutive female breast cancer patients, admitted to the Department of Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal between November 1997 and October 2012, were retrospectively analyzed. Results: Out of the 944 female breast cancer patients, 263 (27.9%) were <40 years. The mean age was $34.6{\pm}5.0$ years among younger patients compared to $54.1{\pm}9.9$ for those ${\geq}40$ years. The mean age at menarche was also significantly lower ($13.5{\pm}1.5$ vs $14.2{\pm}1.5$ years p=0.001) while the mean duration of symptoms was significantly longer (7.6 vs 6.5 months p=0.004). Family history of breast cancer was evident in 3.0% of the young women versus 0.3% in the older one. Mammography was performed less frequently in younger patients (59.7%), compared to older (74.4%), and was of diagnostic benefit in only 20% of younger patients compared to 85% of older ones. At diagnosis, the mean tumor diameter was significantly larger in young women ($5.0{\pm}2.5$ vs $4.5{\pm}2.4cm$, p=0.005). Axillary lymph nodes were positive in 73% of younger patients and 59% of older patients. In the younger group, the proportion of stage III or IV disease was higher (55.1% vs 47.1%, $p{\leq}0.05$). The proportion of breast conserving surgery was higher in young patients (25.1% vs 8.7%) and a higher proportion of younger patients receive neoadjuvant chemotherapy (9.9% vs 2.8%). The most common histological type was ductal carcinoma (93.1% vs 86%). The proportion of histological grade II or III was higher in younger patients (55.9% vs 24.5%). Similarly, in the younger group, lymphatic and vascular invasion was more common (63.2% vs 34.3% and 39.8% vs 25.4%, respectively). Patients in the younger age group exhibited lower estrogen and/or progesterone receptor positivity (34.7% vs 49.8%). Although statistically not significant, the proportion of triple negative tumors in younger age group was higher (22.4% vs 13.6%). Conclusions: Breast cancer in young Nepalese women represents over one quarter of all female breast cancers, many being diagnosed at an advanced stage. Tumors in young women exhibit more aggressive biological features. Hence, breast cancer in young women is worth special attention for earlier detection.

• Journal of Gastric Cancer
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• 제6권4호
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• pp.277-283
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• 2006

목적: 위암환자에서 위절제술 시행 시 절제연거리가 종양의 특성에 따라 재발률, 재발양상 및 예후에 어떠한 영향을 미치는지 명확히 알려져 있지 않다. 연구자들은 이런 관점에서 분석하여 보다 적극적인 치료가 필요한 대상환자를 선별하여 맞춤치료의 기준을 찾고자 한다. 대상 및 방법: 본원에서 1992년 6월부터 2005년 12월까지 위암으로 위절제술을 시행 받은 환자 중 절제연 암침윤 음성이었던 4,472명을 대상으로 후향적 연구를 시행하였다. 추적기간 중앙값은 37개월($1{\sim}162$개월)이었다. 결과: 조기위암 환자군에서 절제연거리가 2 cm 미만인 군과 이상인 군 사이에 재발률, 재발양상 및 5년 생존율에 차이가 없었다. 진행위암 환자는 절제연거리 3 cm를 기준으로 분류하였을 때 그 이상인 경우와 미만인 환자군의 생존율에 의미있는 차이가 있었다(P=0.02). 진행위암 환자 중 미만형, 위하부 1/3 위암, Borrmann 3, 4형은 절제연거리가 3 cm 이상인 군이 미만인 군에 비해 생존율의 의미 있는 차이를 보였다(P<0.05). 생존율에 영향을 미치는 인자는 다변량 생존분석 결과 연령, 병기, 수술방법, Borrmann형, 근치도가 독립적인 인자였다. 결론: 위암환자에서 위절제술 시행 시 종양의 변연부와 근위부 위절제연까지의 거리는 조기위암의 경우 재발률 및 생존율에 영향을 미치는 의미 있는 인자로 생각되지 않으며, 진행위암은 미만형, 하부 1/3, Borrmann 3, 4형의 경우에는 절제연을 3 cm 이상 확보하는 것이 환자의 생존율 향상에 중요할 것으로 판단된다.

• 대한두경부종양학회지
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• 제21권1호
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• pp.3-9
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• 2005

Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.

• The Korean Journal of Physiology and Pharmacology
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• 제23권3호
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• pp.171-179
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• 2019

Pituitary tumors are usually benign but can occasionally exhibit hormonal and proliferative behaviors. Dysregulation of the G1/S restriction point largely contributes to the over-proliferation of pituitary tumor cells. F-box protein S-phase kinase-interacting protein-2 (SKP2) reportedly targets and inhibits the expression of $p27^{Kip1}$, a well-known negative regulator of G1 cell cycle progression. In this study, SKP2 expression was found to be upregulated while $p27^{Kip1}$ expression was determined to be downregulated in rat and human pituitary tumor cells. Furthermore, SKP2 knockdown induced upregulation of $p27^{Kip1}$ and cell growth inhibition in rat and human pituitary tumor cells, while SKP2overexpression elicited opposite effects on $p27^{Kip1}$ expression and cell growth. The expression of microRNA-186 (miR-186) was reported to be reduced in pituitary tumors. Online tools predicted SKP2 to be a direct downstream target of miR-186, which was further confirmed by luciferase reporter gene assays. Moreover, miR-186 could modulate the cell proliferation and $p27^{Kip1}$-mediated cell cycle alternation of rat and human pituitary tumor cells through SKP2. As further confirmation of these findings, miR-186 and $p27^{Kip1}$ expression were downregulated, while SKP2 expression was upregulated in human pituitary tumor tissue samples; thus, SKP2 expression negatively correlated with miR-186 and $p27^{Kip1}$ expression. In contrast, miR-186 expression positively associated with $p27^{Kip1}$ expression. Taken together, we discovered a novel mechanism by which miR-186/SKP2 axis modulates pituitary tumor cell proliferation through $p27^{Kip1}$-mediated cell cycle alternation.

• Journal of Chest Surgery
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• 제55권1호
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• pp.10-19
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• 2022

Background: According to the eighth TNM (tumor-node-metastasis) staging system, the presence of separate tumor nodules in the same lobe is designated as a T3 descriptor. However, it remains unclear whether adjuvant chemotherapy confers survival advantages in this setting. Methods: We retrospectively identified 142 pathologic T3N0M0 patients with additional pulmonary nodules in the same lobe from a single-institutional database from 2004 to 2019. The main outcomes were overall survival and recurrence-free survival. Multivariable Cox regression was used to identify the benefit of adjuvant chemotherapy while adjusting for other variables. Results: Sixty-one patients received adjuvant chemotherapy (adjuvant group) and 81 patients did not receive adjuvant therapy after surgery (surgery-only group). There were no demonstrable differences between the 2 groups regarding hospital mortality and postoperative complications, indicating that treatment selection had not significantly occurred. However, the use of adjuvant chemotherapy was associated with improved 5-year overall survival (70% vs. 59%, p=0.006) and disease-free survival (60% vs. 46%, p=0.040). A multivariable Cox model demonstrated that adjuvant chemotherapy was associated with a survival advantage (adjusted hazard ratio, 0.54; p<0.001). In exploratory analyses of subgroups, the effect of adjuvant chemotherapy seemed to be insufficient in those with small main tumors (<4 cm). Conclusion: Adjuvant chemotherapy was associated with better survival in T3 cancers with an additional tumor nodule in the same lobe. However, the role of adjuvant chemotherapy in patient subgroups with small tumors or those without risk factors should be determined via large studies.

• Korean Journal of Radiology
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• 제22권5호
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• pp.725-734
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• 2021

Objective: To intraindividually compare hepatocellular carcinoma (HCC) washout between MRIs using hepatobiliary agent (HBA) and extracellular agent (ECA). Materials and Methods: This study included 114 prospectively enrolled patients with chronic liver disease (mean age, 55 ± 9 years; 94 men) who underwent both HBA-MRI and ECA-MRI before surgical resection for HCC between November 2016 and May 2019. For 114 HCCs, the lesion-to-liver visual signal intensity ratio (SIR) using a 5-point scale (-2 to +2) was evaluated in each phase. Washout was defined as negative visual SIR with temporal reduction of visual SIR from the arterial phase. Illusional washout (IW) was defined as a visual SIR of 0 with an enhancing capsule. The frequency of washout and MRI sensitivity for HCC using LR-5 or its modifications were compared between HBA-MRI and ECA-MRI. Subgroup analysis was performed according to lesion size (< 20 mm or ≥ 20 mm). Results: The frequency of portal venous phase (PP) washout with HBA-MRI was comparable to that of delayed phase (DP) washout with ECA-MRI (77.2% [88/114] vs. 68.4% [78/114]; p = 0.134). The frequencies were also comparable when IW was allowed (79.8% [91/114] for HBA-MRI vs. 81.6% [93/114] for ECA-MRI; p = 0.845). The sensitivities for HCC of LR-5 (using PP or DP washout) were comparable between HBA-MRI and ECA-MRI (78.1% [89/114] vs. 73.7% [84/114]; p = 0.458). In HCCs < 20 mm, the sensitivity of LR-5 was higher on HBA-MRI than on ECA-MRI (70.8% [34/48] vs. 50.0% [24/48]; p = 0.034). The sensitivity was similar to each other if IW was added to LR-5 (72.9% [35/48] for HBA-MRI vs. 70.8% [34/48] for ECA-MRI; p > 0.999). Conclusion: Extracellular phase washout for HCC diagnosis was comparable between MRIs with both contrast agents, except for tumors < 20 mm. Adding IW could improve the sensitivity for HCC on ECA-MRI in tumors < 20 mm.

• 동의생리병리학회지
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• 제18권3호
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• pp.900-907
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• 2004

The antiproliferative effect of the water extract of the branch and root bark of Ulmi Pumilae Cortex(WEUPC) was investigated on the p53-negative human leukemia cell line (HL-60). A dose- and time-dependent inhibition of cell growth was observed; this effect appears to be due to induction of apoptosis. Involvement of oxidative stress is indicated by a dose-dependent increase in intracellular reactive oxygen species levels. In addition. anti-apoptic effect was observed in the cells simultaneously treated with WEUPC and the anti-oxidant N-acetylcysteine. WEUPC did not affect the anti-apoptotic Bcl-2 and the pro-apoptotic Bax, whereas p21/sup WAF1/CIPl/ was enhanced in a dose- and time-dependent fashion; this effect was partially inhibited by N-acetylcysteine. The increase in p21/sup WAF1/CIPl/ was accompanied by a parallel accumulation of cells in the G1 phase of the cycle. These results suggest that the p53-independent induction of p21/sup WAF1/CIP/ and the induction of apoptosis may mediate the anti proliferative effect of WEUPC at least in this study; on the basis of this observation, WEUPC could be proposed as an useful adjunct to the treatment of p53-deficient tumors, which are often refractory to standard chemotherapy.

• Toxicological Research
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• 제32권3호
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• pp.251-258
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• 2016

Mesenchymal stem cells (MSCs) have been identified in multiple types of tissue and exhibit characteristic self-renewal and multi-lineage differentiation abilities. However, the possibility of oncogenic transformation after transplantation is concerning. In this study, we investigated the tumorigenic potential of umbilical cord blood-derived MSCs (hUCB-MSCs) relative to MRC-5 and HeLa cells (negative and positive controls, respectively) both in vitro and in vivo. To evaluate tumorigenicity in vitro, anchorage-independent growth was assessed using the soft agar colony formation assay. hUCB-MSCs and MRC-5 cells formed few colonies, while HeLa cells formed a greater number of larger colonies, indicating that hUCB-MSCs and MRC-5 cells do not have anchorage-independent proliferation potential. To detect tumorigenicity in vivo, hUCB-MSCs were implanted as a single subcutaneous injection into BALB/c-nu mice. No tumor formation was observed in mice transplanted with hUCB-MSCs or MRC-5 cells based on macro- and microscopic examinations; however, all mice transplanted with HeLa cells developed tumors that stained positive for a human gene according to immunohistochemical analysis. In conclusion, hUCB-MSCs do not exhibit tumorigenic potential based on in vitro and in vivo assays under our experimental conditions, providing further evidence of their safety for clinical applications.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6963-6966
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• 2015

Background: During the past few years, Hesa-A, a herbal-marine mixture, has been used to treat cancer as an alternative medicine in Iran. Based on a series of studies, it is speculated that Hesa-A possesses special cytotoxic effects on invasive tumors. To test this hypothesis, we investigated the selective anticancer effects of Hesa-A on several cancer cell lines with different metastatic potential. Materials and Methods: Hesa-A was prepared in normal saline as a stock solution of 10 mg/ml and further diluted to final concentrations of $100{\mu}/ml$, $200{\mu}g/ml$, $300{\mu}g/ml$ and $400{\mu}g/ml$. MTT-based cytotoxicity assays were performed with A549 (lung non small cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: All treated cancer cells showed significant (P<0.01) or very significant (P<0.0001) differences in comparison to negative control at almost all of the tested doses ($100-400{\mu}g/ml$). At the lower dose ($100{\mu}g/ml$), Hesa-A reduced cell viability to 66%, 45.3%, 35.5%, 33.2% in SKOV3, A549, PC-3 and MCF-7 cells, respectively. Moreover, at the highest dose ($400{\mu}g/ml$), Hesa-A resulted in 88.5%, 86.6%, 84.9% and 79.3% growth inhibition in A549, MCF-7, PC-3 and SKOV3 cells, respectively. Conclusions: Hesa-A exert potent cytotoxic effects on different human cancer cells, especially those with a high metastatic potential.

• Radiation Oncology Journal
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• 제34권4호
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• pp.239-249
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• 2016

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of 'reoxygenation' phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because 'reoxygenation' is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn't it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.