• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.914-921
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• 1997

Hereditary hemorrhagic telangiectasia(Osler-Rendu-Weber Syndrome) is characterized by telangiectasia of the skin and mucous membranes and intermittent bleeding from vascular abnormalities. About 20% of patients with this syndrome have pulmonary arteriovenous fistulas. Pulmonary arteriovenous fistula is uncommon malformation which has an abnormal connection between the pulmonary capillary bed, in which venous blood in the pulmonary artery is shunted through the fistula into the pulmonary vein without exposure to alveolar oxygen and result in unoxygenated, desaturated systemic arterial blood, polycythemia, cyanosis and clubbing. Death often results from cerebral abscess and rupture of the malformation with massive hemorrhage. Therapeutic intervention is recommended for all symptomatic patients because of the risk of those serious complications. Treatment options include surgery and transcatheter obliteration with steel coils or detachable balloons. Therapeutic embolization has the advantages that multiple bilateral pulmonary arteriovenous fistulas can be occluded and also that the procedure can be repeated if necessary. Recently we experienced a case of the multiple bilateral pulmonary arteriovenous fistulas associated with telangiectatic change of hepatic artery and multiple angiodysplasia on the gastric mucosa in 41 years old female patient who had mild dyspnea of exertion(NYHA class II). clubbing finger, severe iron deficiency anemia. She was treated with embolization technique using steel coils and iron replacement. After the therapeutic embolization. significant improvement of dyspnea of exertion with disappearance of multiple pulmonary nodule on follow-up simple chest x-ray was noted. During the subsequent six months follow-up period, she had the improvement of symptoms and iron deficiency anemia.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.26-30
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• 2015

Wnt/${\beta}$-catenin signaling pathway was mutated in about 90% of the sporadic and hereditary colorectal cancers. The abnormally activated ${\beta}$-catenin increases the cancer cell proliferation, differentiation and metastasis through increasing the expression of its oncogenic target genes. In this study, we identified an inhibitor of ${\beta}$-catenin dependent Wnt pathway from rhizomes of Atractylodes macrocephala Koidzumi (Compositae). The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC). AC suppressed b-catenin/Tcell factor transcriptional activity of HEK-293 reporter cells when they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-$3{\beta}$. AC down-regulated the nuclear level of ${\beta}$-catenin through the suppression of galectin-3 mediated nuclear translocation of ${\beta}$-catenin in SW-480 colon cancer cells. Furthermore, AC inhibits proliferation of colon cancer cell. Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

• Journal of Gastric Cancer
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• v.10 no.4
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• pp.149-154
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• 2010

Purpose: Replication error is an important mechanism in carcinogenesis. The microsatellite instability (MSI-H) of colorectal cancers is associated with the development of multiple cancers. The influence of MSI-H on the development of multiple gastric cancers in sporadic gastric cancer patients has not been defined. This study was performed to reveal the association between the clinicopathologic features and MSI in sporadic gastric cancers. Materials and Methods: Between July 2004 and March 2009, the clinicopathologic characteristics, including MSI status, were evaluated in 128 consecutive patients with sporadic gastric cancers. None of the patients had hereditary non-polyposis colorectal cancer of familial gastric cancer. The markers that were recommended by the NCI to determine the MSI status for colorectal cancers were used Results: MSI-H cancers were found in 10.9% of the patients (14/128). Synchronous gastric cancers were shown in 4 patients (3.1%). Synchronous cancers were found in 2 of 14 patients with MSI-H gastric cancer (14.3%) and 2 of 114 patients with MSS gastric cancer (1.8%; P=0.059, Fisher's exact test). Among the patients with synchronous cancer 50% (2/4) had MSI-H cancer, but 9.7% of the patients (12/124) without synchronous cancer had MSI-H cancer. MSI-H (RR, 24.7; 95% CI, 1.5~398.9; P=0.024) was related with to synchronous gastric cancer, but age, gender, family history, histologic type, location, gross morphology, size, and stage were not related to synchronous gastric cancer. Conclusions: MSI is associated with the intestinal-type gastric cancer and the presence of multiple gastric cancers in patients with sporadic gastric cancer. Special attention to the presence of synchronous and the development of metachronous multiple cancer in patients with MSI-H gastric cancer is needed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2141-2144
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• 2014

Background: Gastric cancer is the second most common cause of cancer death. It has a poor prognosis with only 5-10% of hereditary etiology. If it is diagnosed, it could be helpful for screening the other susceptible members of a family for preventive procedures. Usually it is identified by symptoms such as presence of cancer in different members of family, some special type of pathology such as diffused adenocarcinoma, having younger age and multiple cancer syndromes. Hence, designing a registry program can be a more practical way to screen high risk families for a preventive program. Materials and Methods: Based on the inclusion criteria, a questionnaire was prepared. After pilot on a small number of patients, the actual data was collected from 197 patients and processed in SPSS 16.0. Results: Totally, 11.8% of the patients were younger than 45 years old. Blood type 'A' was dominant and males had a higher risk behavior with higher consumption of unhealthy food. Adenocarcinoma was reported in majority of cases. 21.8% of the patients had the including criteria for familial gastric cancer (FGC). Conclusions: The high percentage of FGC population compared to the other studies have revealed a need to design an infrastructural diagnostic protocol and screening program for patients with FGC, plus preventive program for family members at risk which could be done by a precise survey related to frequency and founder mutations of FGC in a national registry program.

• Biomedical Science Letters
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• v.9 no.3
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• pp.171-175
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• 2003

Microsatellite instability (MSI), which is caused by a deficient mismatch repair system, is seen in most of the hereditary non-polyposis colon cancers (HNPCC) and a portion of sporadic colorectal cancers. Forty unselected colorectal cancer patients were analyzed for MSI using silver stain plus kit. The overall incidence of MSI in studied cases was 17％ (7/40). The incidence is similar result with previous study. MSI in colorectal carcers was more prevalent in moderative differentiated adenocarcinoma than well differentiated adenocarcinoma

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7929-7933
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• 2015

Background: The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in females, pushing the cervical cancer to the second position. Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2. Alterations in these genes have been reported in different populations, some of which are population-specific mutations showing founder effects. Two specific mutations in the BRCA1 (185delAG) and BRCA2 (6174delT) genes have been reported to be of high prevalence in different populations. The aim of this study was to estimate the carrier frequency of 185delAG and 6174delT mutations in eastern Indian breast cancer patients. Materials and Methods: We selected 231 histologically confirmed breast cancer patients from our tertiary cancer care center in eastern India. Family history was obtained by interview or a self-reported questionnaire. The presence of the mutation was investigated by allele specific duplex/multiplex-PCR on genomic DNA extracted from peripheral blood. Results: A total of 231 patients (age range: 26-77 years), 130 with a family history and 101 without were screened. The two founder mutations 185delAG in BRCA1 and 6174delT in BRCA2 were not found in any of the subjects. This was confirmed by molecular analysis. Conclusions: Our findings suggest that these BRCA mutations may not have a strong recurrent effect on breast cancer among the eastern Indian population. The contribution of these founder mutations to breast cancer incidence is probably low and could be limited to specific subgroups. This may be particularly useful in establishing further pre-screening strategies.

• Journal of Genetic Medicine
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• v.10 no.2
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• pp.124-127
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• 2013

Among cause of carcinogenesis, heredity is believed to take about 10 percent in ovarian cancer. BRCA1 or BRCA2 account for largest portion of Hereditary Breast and Ovary Cancer (HBOC). Frequency of BRCA1/2 germ line mutations varies according to region and ethnicity from 1.1-39.7 percent. The identification of ovarian cancers with a BRCA mutation is will be more and important due to the possibility to offer a genetic counseling and also due to potential beneficial treatment effects with a poly-ADP-ribose polymerase inhibitor in some individuals. We report the case of a 41 year old woman with a stage Ic mucinous ovarian adenocarcinoma and carrier daughter found on family genetic counseling. We indentified other family members with a history of breast cancer of 1st degree and pancreatic cancer of 2nd degree relative. After a screening with immunohistochemistry, the absence of nuclear expression for BRCA1 and BRCA2 was revealed. The gene sequencing confirmed heterozygous mutations of BRCA2 gene. The daughter of the case subject consented for a test. This test was shown the daughter is positive for BRCA2 mutation. Regular surveillance, chemoprophylaxis with oral contraceptive and prophylactic surgery after childbearing were offered to her.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.619-624
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• 2013

Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

• Advances in pediatric surgery
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• v.12 no.1
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• pp.24-31
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• 2006

Hereditary pancreatitis (HP) appears as an autosomal dominant trait. If the patient has (1) more than 2 affected relatives in different generations and (2) no known etiological factors such as alcohol or gallstones, or has R122H or N29I mutation in the cationic trypsinogen (CT) gene, the diagnosis of HP can be applied. Risk of pancreatic cancer is estimated to be 53-fold higher than in a general population after the age of 50 years. We report a kindredof HP, involving three of its family together; two siblings (14 years old, 13 years old) and cousin (26 years old). The patient had complicating chronic pancreatitis and pancreatic stone, and was treated with amodified Puestow-Gillesby procedure. Her sisters showed chronic pancreatitis. Her cousin underwent a drainage procedure of the pancreatic duct for chronic pancreatitis during the high school period. All the three members showed the R122H mutation of the CT gene.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4013-4016
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• 2012

Purpose: Breast cancer is the commonest malignancy of females throughout the world with one million new cases each year. In Pakistan, the burden of breast cancer disease is high with late stage presentation being a common feature, more than half being stage III or stage IV. The objective of this study was to study various aspects, patterns and risk factors in breast cancer patients of Balochistan. Method: Present study was performed on 134 patients of breast cancer who were registered in CENAR. The patients were interviewed by providing a questionnaire. Informed consent was taken from all the patients who took part in this study after explanation of the study aims. Body mass index (BMI) was calculated andbiopsy reports were obtained from patients files. All the cases were classified with respect to age, gender, ethnic group (Baloch, Pashtoon, Punjabi, Afghani, Hazara) BMI, cancer type, cancer grade, hormonal status, side of the cancer, fertility and marital status. Results: Out of 134 patients, the most common ethnic group was Pashtoon with a total of 42 and the common age group was 41-50 years with a total of 51. Invasive ductal carcinoma (IDC) was the most common type, accounting for in 128 patients (95.5%) followed by invasive lobular carcinoma (ILC). Conclusion: Pashtoon was the most common ethnic group, IDC was common type and most of the patients had an ER/PR positive hormonal status.