• Journal of Digestive Cancer Research
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• v.4 no.2
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• pp.122-126
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• 2016

Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. The most common cancers involving the leptomeninges are breast, lung cancer and melanoma. However, gastric adenocarcinoma has been rarely reported with leptomeningeal carcinomatosis. The presenting manifestations are usually headache, visual disturbances and seizures. We report a case of leptomeningeal metastasis that presented as a gastric cancer. A 75-year old man was transferred to our hospital for further evaluation and treatment after being diagnosed with adenocarcinoma through endoscopic biopsy during a regular health examination. An abdominal computed tomography (CT) showed AGC, stage IA (cT1N0M0), while an endoscopic examination showed AGC, Borrmann type 2. The patient is currently under observation after undergoing radical subtotal gastrectomy with gastroduodenostomy and subsequent administration of oral chemotherapeutic agents. As an abdominal CT response assessment performed after surgery revealed new metastasis to the liver, the patient received palliative chemotherapy as recurrence was suspected. After receiving chemotherapy in the order of DP (Cisplatin + Docetaxel), FOLFIRI (5-FU + Leucovorin + Irinotecan), an abdominal CT response assessment showed complete response. Since decreased mentality maintained throughout the follow up period based on outpatient clinic, brain MRI was performed and revealed multiple leptomeningeal metastasis. The Patient died 2 days after the diagnosis.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.186-191
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• 2004

Primary small-cell carcinomas of the stomach are rare and aggressive malignancies with poor survival rates. Preoperative diagnosis is difficult and a standard treatment is not yet established. We have recently experienced two cases of a primary small-cell carcinoma of the stomach. The first case was a 65-year-old man with epigastric soreness. Endoscopic biopsy showed an adenocarcinoma. He underwent a radical subtotal gastrectomy with D2 lymph-node dissection. Pathology revealed a collision tumor of a smallcell carcinoma and an adenocarcinoma with submucosal invasion and with metastasis in 20 out of 48 lymph nodes (T1N3M0). The second case was a 64-year-old man with epigastric soreness. Endoscopic biopsy revealed a small-cell carcinoma. There was no evidence of a primary tumor in the lung. A radical subtotal gastrectomy with D2 lymph-node dissection was performed. Pathology showed a pure smallcell carcinoma with proper muscle invasion and with metastasis in 1 out of 36 lymph nodes (T2aN1M0).

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5703-5707
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• 2015

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of their antioxidative properties. Melissa officinalis L. (MO), an aromatic and medicinal plant, is well known in thios context. However, toxicity against cancer cells has not been fully studied. Here, we investigated the selective anticancer effects of an MO extract (MOE) in different human cancer cells. Materials and Methods: a hydro-alcoholic extract of MO was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. MTT assays were used to evaluate cytotoxicity of different doses of MOE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer cells), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, MOE reduced the cell viability to values below 33%, even at the lowest doses. In all cases, $IC_{50}$ values were below $5{\mu}g/ml$. The mean growth inhibition was 73.1%, 86.7%, 79.9% and 77.8% in SKOV3, MCF-7 and PC-3 and A549 cells, respectively. Conclusions: Our results indicate that a hydro-alcoholic extract of MO possess a high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important than a maximally tolerated one. Moreover, the antiprolifreative effect of MO seems to be tumor type specific, as hormone dependant cancers were more sensitive to antitumoral effects of MOE.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1119-1122
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• 2016

Background: Punica granatum (PG) has been demonstrated to possess antitumor effects on various types of cancer cells. In this study, we determined antiproliferative properties of a seed extract of PG (PSE) from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate seeds was prepared. Total phenolic content (TPC) and total flavonoid content (TFC) were assessed by colorimetric assays. Antioxidant activity was determined with reference to DPPH radical scavenging activity. The cytotoxicity of different doses of PSE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell carcinoma), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all studied cancer cells, PSE reduced the cell viability to values below 23%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, SKOV3 ovarian cancer cells were the most responsive to antiproliferative effects of PSE with a maximum mean growth inhibition of 86.8% vs. 82.8%, 81.4% and 80.0% in MCF-7, PC-3 and A549 cells, respectively. Conclusions: Low doses of PSE exert potent antiproliferative effects on different human cancer cells SKOV3 ovarian cancer cells as most and A549 cells ar least responsive regarding cytotoxic effects. However, the mechanisms of action need to be addressed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5727-5731
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• 2015

Background: There is a long standing interest in natural compounds especially those with a high polyphenolic content and high scavenging activity for hazardous free radicals. Cornus mas (CM) fruit is well known for its antioxidant activities; however, its toxicity against human cancers needs to be addressed. Here, we investigated selective anticancer effects of CM on different human cancer cells. Materials and Methods: A hydro-alcoholic extract of CM (HECM) was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was assessed with respectto DPPH radical scavenging. MTT assays were used to evaluate the cytotoxicity of different doses of CM (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer) and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.05) or very significant (P<0.001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, HECM reduced the cell viability to values below 26%, even at the lowest doses. In all cases, $IC_{50}$ was obtained at doses below $5{\mu}g/ml$. The mean growth inhibition was 81.8%, 81.9%, 81.6% and 79.3% in SKOV3, MCF-7, PC-3 and A549 cells, respectively. Conclusions: Altogether, to our best knowledge, this is a first study that evaluated toxicity of a HECM with high antioxidant activity in different human cancer cells in vitro. Our results indicated that a hydro-alcoholic extract of CM possesses high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important and relevant than a maximally tolerated one.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.2
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• pp.248-261
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• 2024

Backgrounds/Aims: This study aimed to investigate patterns and factors affecting recurrence after curative resection for pancreatic ductal adenocarcinoma (PDAC). Methods: Consecutive patients who underwent curative resection for PDAC (2011-21) and consented to data and tissue collection (Barts Pancreas Tissue Bank) were followed up until May 2023. Clinico-pathological variables were analysed using Cox proportional hazards model. Results: Of 91 people (42 males [46%]; median age, 71 years [range, 43-86 years]) with a median follow-up of 51 months (95% confidence intervals [CIs], 40-61 months), the recurrence rate was 72.5% (n = 66; 12 loco-regional alone, 11 liver alone, 5 lung alone, 3 peritoneal alone, 29 simultaneous loco-regional and distant metastases, and 6 multi-focal distant metastases at first recurrence diagnosis). The median time to recurrence was 8.5 months (95% CI, 6.6-10.5 months). Median survival after recurrence was 5.8 months (95% CI, 4.2-7.3 months). Stratification by recurrence location revealed significant differences in time to recurrence between loco-regional only recurrence (median, 13.6 months; 95% CI, 11.7-15.5 months) and simultaneous loco-regional with distant recurrence (median, 7.5 months; 95% CI, 4.6-10.4 months; p = 0.02, pairwise log-rank test). Significant predictors for recurrence were systemic inflammation index (SII) ≥ 500 (hazard ratio [HR], 4.5; 95% CI, 1.4-14.3), lymph node ratio ≥ 0.33 (HR, 2.8; 95% CI, 1.4-5.8), and adjuvant chemotherapy (HR, 0.4; 95% CI, 0.2-0.7). Conclusions: Timing to loco-regional only recurrence was significantly longer than simultaneous loco-regional with distant recurrence. Significant predictors for recurrence were SII, lymph node ration, and adjuvant chemotherapy.

• Molecules and Cells
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• v.45 no.10
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• pp.718-728
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• 2022

Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

• Journal of Chest Surgery
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• v.23 no.1
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• pp.81-89
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• 1990

A total of 178 patients with primary lung cancer who had undergone complete resection of the tumor in combination with complete mediastinal lymphadenectomy were reviewed at the Department of Thoracic and Cardiovascular Surgery of Yonsei Medical Center from January 1980 through July 1989. Materials; 1. There were 45 men and 33 women ranging of age from 25 to 78 years with a mean age of 55.4 years. 2. Histological types were squamous carcinoma in 115 cases [64.6%] adenocarcinoma in 42 cases [23.6 %], bronchioloalveolar carcinoma in 9 cases [5.1%], large cell carcinoma in 8 cases [4.5 %] and small cell carcinoma in 4 cases [2.2%] Results were summarized as follows: 1. The size of primary tumor was not directly proportional to the frequency of mediastinal lymph node metastasis. [P =0.0567] 2. The histologic types of the primary tumor did not related to the incidence of mediastinal lymph node metastasis. [P >0.19] 3. The chance of mediastinal lymph node metastasis in the case with lung cancer located in right middle lobe[31.8%, N=22] and left lower lobe [31.4%, N=32] were the highest and the lowest was the one located in right lower lobe, while over all incidence of mediastinal lymph node metastasis in this series was 25.4 % [N=55]. 4. The rate of mediastinal lymph node metastasis without evidence of regional and hilar lymph node metastasis was 13%. [N=23] The chance of mediastinal lymph node involvement without N1 lymph node metastasis was 16.3 % [N=17] in both upper lobes and 8.2 % [N=6] in both lower lobes. It was statistically significant that the tumors in the upper lobes had greater chance of the mediastinal lymph node metastasis without N1 than the tumors in the lower lobes. 5. In this series majority of the patients with lung cancer the mediastinal lymph node metastasis from the tumor in each pulmonary lobes usually occurs via ipsilateral tracheobronchial and paratracheal lymphatic pathway. Especially the lung cancer located in lower lobes can metastasize to subcarinal, paraesophageal and inferior pulmonary ligamental lymph node through the lymphatic pathway of inferior pulmonary ligament. It can be speculated that in some cases of this series otherwise mediastinal lymph node metastasis can also occur with direct invasion to the parietal pleura and to the mediastinal lymph node via direct subpleural lymphatic pathway .

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.980-985
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• 2000

A 52-year-old woman was presented with 2-week history of increasing dyspnea and dry cough. The chest radiograph revealed bilateral reticular infiltrates. Radiographic infiltrates were rapidly progressed and symptoms from hypoxemia were aggravated. The patient was intubated and bronchoscopy with transbronchial lung biopsies was performed. Biopsies revealed lymphatic vessels plugged by nests of metastatic adenocarcinoma. She died 11 days after admission despite of intensive ventilatory support. We had difficulties in the diagnosis of lymphangitic lung carcinomatosis at initial presentation of her illness because the progression was unusually rapid. Lymphangitic lung carcinomatosis shoud should be included in the differential diagnosis of patients showing rapidly progressive interstitial radiographic findings. Also, transbronchial biopsy may be a useful tool to confirm the diagnosis.