INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relatio...INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].展开更多
AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC). METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and ...AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC). METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020, S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT. Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and beta-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil (Ver) and indomethacin (IMC), respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay. RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT(19 and 9.5-fold to their parental cell line SUIT-2, respectively). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2, the levels of beta-tubulin isotype II, III expressions in S-2/TXT were increased remarkably. CONCLUSION: The both intrinsic and acquired TXT-related drug resistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP expressions. The increases of beta-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT.展开更多
Background:Shadow cells, characterized by basaloid squamous cells with a distinct well-defined border and a central unstained area as a shadow of lost nuclei, are characteristic of pilomatricoma, a distinct neoplasm o...Background:Shadow cells, characterized by basaloid squamous cells with a distinct well-defined border and a central unstained area as a shadow of lost nuclei, are characteristic of pilomatricoma, a distinct neoplasm of hair matrix differentiation. The presence of shadow cells within tumor islands composed of follicular germinative cells of an otherwise classic basal cell carcinoma (BCC) has been considered as a distinct diagnostic category of BCC with matrical differentiation. We present a case of BCC with matrical differentiation in a trans-plant patient. To our knowledge, only 10 cases [Aloi et al. Am J Dermatopathol 1988; 10:509; Ambrojo et al. Am J Dermatopathol 1992; 14:293; Sagol et al. East J Med 1999; 4:37; Kwittken J. Cutis 2002; 69:57; Kim et al. Yonsei Med J 2003; 44:523]of BCC showing matrical differentiation have been reported. None have been reported arising on the background of immunosuppression. Methods:A 58-year-old male cardiac transplant patient with a nodule on the dorsum of left hand was studied. It arose and enlarged rapidly within a few months, causing irritation and bleeding. The nodule was surgically excised and submitted for histopathologic evaluation. The sections were prepared by hematoxylin and eosin (H&E) method. Results:The H&E-stained sections of the hand lesion revealed multiple nodular masses of basaloid follicular germinative cells. In some areas, there was peripheral palisading and stromal retraction artifact typical of classic BCC. In these areas, the tumor nodules were connected to the epidermis, whereas in others, it extended deep into the reticular dermis to the subcutaneous fat junction. Elsewhere, the majority of the tumor contained a population of shadow cells, similar to those in pilomatricoma, with basaloid-appearing matrical cells in the periphery. Trichohyaline granules were identified in the cytoplasm of many of the peripheral asaloid cells. These granules are one of the characteristic features of follicular matrix differentiation. Mitoses were rare. Areas of cystic degeneration were present throughout the tumor. There was no evidence of an infiltrating gro wth pattern, lymphovascular invasion, or sarcomatoid growth pattern. Conclusion :BCC with matrical differentiation is a distinct pathologic entity and a rare s ubtype of BCC featuring shadow and matrical cells, typically seen in pilomatrico ma, a benign hair matrix neoplasm. This tumor has not yet been reported in an im munosuppressed transplant patient.展开更多
Objective. -To evaluate the frequency of menorrhagia and endometriosis in female migraineurs compared to age-matched women without headache. Background. -Migraine predominantly affects women of childbearing age and is...Objective. -To evaluate the frequency of menorrhagia and endometriosis in female migraineurs compared to age-matched women without headache. Background. -Migraine predominantly affects women of childbearing age and is often associated with the menstrual period, yet there is a paucity of data regarding the relationship of migraine and menstrual disorders. Methods. -Women diagnosed with migraine, using International Headache Society criteria and an age-and sex-matched control group, were administered a semistructured questionnaire regarding migraine and migraine-related disability, menstrual history, other bleeding history, vascular event history, and vascular risk factors. Results. -Fifty female migraineurs between the ages of 22 and 50 years and 52 age-matched women (mean age 37 years) were enrolled in the study. Similar proportions of women in each group reported using hormone contraceptives (30%vs. 33%, P= .77) and hormone replacement therapy (12%vs. 8%, P= .69). The proportions presently menstruating (64 %vs. 80%, P= .20) and status after hysterectomy were similar (24%vs. 14%, P= .84). Menorrhagia (defined as at least three consecutive heavy periods), both current and prior, was more commonly reported in migraineurs (63%vs. 37%, P=.009), with higher likelihood of staining clothes by menses (35%vs. 8%, P= .003), and significant impact of menses on activities of daily living (on a 10-point Likert scale) with work/school participation (P= .02), family activities (P < .0001), sleep (P= .003), life enjoyment (P= .001), mood (P= .02), and overall quality of life (P= .003). Endometriosis, which may be associated with menorrhagia, was also more commonly diagnosed in the migraineurs (30%vs. 4%, P= .001). The migraineurs more frequently described bruising (40%vs. 10%, P < .001) and rectal bleeding (18%vs. 2%, P= .017) but not more serious bleeding problems. Nonsteroidal anti-inflammatory drug (NSAID) use was more frequent in the migraine group (28%vs. 12%, P= .036), and significance for increased menorrhagia, endometriosis, menstrual interference, and bruising was maintained, even when controlling for the use of NSAIDs. With logistic regression, menorrhagia was significantly associated with migraine, adjusted odds ratio (OR) = 2.8 (95%CI 1.2 to 6.5), and with endometriosis, adjusted OR = 10.5 (95%CI 2.2 to 51.4). There were no differences in vascular events and risk factors, except for trends of increased hypertension (25%vs. 10%, P= .05), transient ischemic attack/stroke (10%vs. 2%, P= .08), and Raynaud’s disease (10%vs. 2%, P= .08) in the migraineurs. Conclusion. -Women with migraine have a higher frequency of menorrhagia, endometriosis, and associated psychosocial consequences. These findings suggest that there should be further study of factors influencing endometriosis and menstrual blood flow, such as eicosanoids and platelet function, in migraineurs.展开更多
基金Supported in part by phone-Poulenc Rorer Pharmaceuticals INC
文摘INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].
基金Supported in part by Phne-Poulenc Rorer Pharmaceuticals INC.
文摘AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC). METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020, S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT. Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and beta-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil (Ver) and indomethacin (IMC), respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay. RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT(19 and 9.5-fold to their parental cell line SUIT-2, respectively). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2, the levels of beta-tubulin isotype II, III expressions in S-2/TXT were increased remarkably. CONCLUSION: The both intrinsic and acquired TXT-related drug resistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP expressions. The increases of beta-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT.
文摘Background:Shadow cells, characterized by basaloid squamous cells with a distinct well-defined border and a central unstained area as a shadow of lost nuclei, are characteristic of pilomatricoma, a distinct neoplasm of hair matrix differentiation. The presence of shadow cells within tumor islands composed of follicular germinative cells of an otherwise classic basal cell carcinoma (BCC) has been considered as a distinct diagnostic category of BCC with matrical differentiation. We present a case of BCC with matrical differentiation in a trans-plant patient. To our knowledge, only 10 cases [Aloi et al. Am J Dermatopathol 1988; 10:509; Ambrojo et al. Am J Dermatopathol 1992; 14:293; Sagol et al. East J Med 1999; 4:37; Kwittken J. Cutis 2002; 69:57; Kim et al. Yonsei Med J 2003; 44:523]of BCC showing matrical differentiation have been reported. None have been reported arising on the background of immunosuppression. Methods:A 58-year-old male cardiac transplant patient with a nodule on the dorsum of left hand was studied. It arose and enlarged rapidly within a few months, causing irritation and bleeding. The nodule was surgically excised and submitted for histopathologic evaluation. The sections were prepared by hematoxylin and eosin (H&E) method. Results:The H&E-stained sections of the hand lesion revealed multiple nodular masses of basaloid follicular germinative cells. In some areas, there was peripheral palisading and stromal retraction artifact typical of classic BCC. In these areas, the tumor nodules were connected to the epidermis, whereas in others, it extended deep into the reticular dermis to the subcutaneous fat junction. Elsewhere, the majority of the tumor contained a population of shadow cells, similar to those in pilomatricoma, with basaloid-appearing matrical cells in the periphery. Trichohyaline granules were identified in the cytoplasm of many of the peripheral asaloid cells. These granules are one of the characteristic features of follicular matrix differentiation. Mitoses were rare. Areas of cystic degeneration were present throughout the tumor. There was no evidence of an infiltrating gro wth pattern, lymphovascular invasion, or sarcomatoid growth pattern. Conclusion :BCC with matrical differentiation is a distinct pathologic entity and a rare s ubtype of BCC featuring shadow and matrical cells, typically seen in pilomatrico ma, a benign hair matrix neoplasm. This tumor has not yet been reported in an im munosuppressed transplant patient.
文摘Objective. -To evaluate the frequency of menorrhagia and endometriosis in female migraineurs compared to age-matched women without headache. Background. -Migraine predominantly affects women of childbearing age and is often associated with the menstrual period, yet there is a paucity of data regarding the relationship of migraine and menstrual disorders. Methods. -Women diagnosed with migraine, using International Headache Society criteria and an age-and sex-matched control group, were administered a semistructured questionnaire regarding migraine and migraine-related disability, menstrual history, other bleeding history, vascular event history, and vascular risk factors. Results. -Fifty female migraineurs between the ages of 22 and 50 years and 52 age-matched women (mean age 37 years) were enrolled in the study. Similar proportions of women in each group reported using hormone contraceptives (30%vs. 33%, P= .77) and hormone replacement therapy (12%vs. 8%, P= .69). The proportions presently menstruating (64 %vs. 80%, P= .20) and status after hysterectomy were similar (24%vs. 14%, P= .84). Menorrhagia (defined as at least three consecutive heavy periods), both current and prior, was more commonly reported in migraineurs (63%vs. 37%, P=.009), with higher likelihood of staining clothes by menses (35%vs. 8%, P= .003), and significant impact of menses on activities of daily living (on a 10-point Likert scale) with work/school participation (P= .02), family activities (P < .0001), sleep (P= .003), life enjoyment (P= .001), mood (P= .02), and overall quality of life (P= .003). Endometriosis, which may be associated with menorrhagia, was also more commonly diagnosed in the migraineurs (30%vs. 4%, P= .001). The migraineurs more frequently described bruising (40%vs. 10%, P < .001) and rectal bleeding (18%vs. 2%, P= .017) but not more serious bleeding problems. Nonsteroidal anti-inflammatory drug (NSAID) use was more frequent in the migraine group (28%vs. 12%, P= .036), and significance for increased menorrhagia, endometriosis, menstrual interference, and bruising was maintained, even when controlling for the use of NSAIDs. With logistic regression, menorrhagia was significantly associated with migraine, adjusted odds ratio (OR) = 2.8 (95%CI 1.2 to 6.5), and with endometriosis, adjusted OR = 10.5 (95%CI 2.2 to 51.4). There were no differences in vascular events and risk factors, except for trends of increased hypertension (25%vs. 10%, P= .05), transient ischemic attack/stroke (10%vs. 2%, P= .08), and Raynaud’s disease (10%vs. 2%, P= .08) in the migraineurs. Conclusion. -Women with migraine have a higher frequency of menorrhagia, endometriosis, and associated psychosocial consequences. These findings suggest that there should be further study of factors influencing endometriosis and menstrual blood flow, such as eicosanoids and platelet function, in migraineurs.
