Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic stem-cell transplants

To examine whether donor-derived cells could exist in nonhematopoietic tissues of recipients after allogeneic hematopoietic stem-cell transplantation, we examined the patterns of the short tandem repeat (STR) of DNA extracted from fingernail clippings of recipients so that the contamination of blood cells was excluded. All 21 patients reached donor-derived hematopoiesis after transplantation and 20 of them were in remission of the primary diseases at the time of sampling. Compared with the STRs of donor cells, among 9 of 21 patients, DNA extracted from fingernail samples showed coexistence of the donor pattern of the STRs, sharing from 8.9% to 72.9% of total STR areas. Time from transplantation to sampling was from 305 to 2399 days among positive cases. These results demonstrate for the first time the existence of stable contribution of donor cells in fingernails among recipients of allogeneic hematopoietic stem cells.     

von Willebrand factor type D domain mutant of SVS-1/SUSD2, vWD(m), induces apoptosis in HeLa cells

SVS-1/SUSD2 is a novel gene, which inhibits growth and reverses tumorigenic phenotypes of cancer cells in vitro. Here we report identification of a mutant of SVS-1, designated SVS-1-vWD(m), in which conserved amino acids GLLG at positions 591-594 in von Willebrand factor type D (vWD) domain are replaced by AAAA. As observed by laser confocal microscope, intracellular localization of the mutant protein has changed such that both the N-terminus and the C-terminus of SVS-1-vWD(m) were localized in the inner surface of the plasma membrane, whereas the N-terminus of SVS-1 was localized in the outer surface of the plasma membrane. Additionally, SVS-1-vWD(m) was processed much less efficiently and in a slightly different manner. In in vitro studies, adenovirus-mediated transduction of the SVS-1-vWD(m)gene induced growth suppression of HeLa cells in a dose-dependent manner, as the wild-type gene and inhibition of anchorage-independent growth. Of great interest is the finding that the mutant protein, vWD(m), but not the wild-type one induced apoptosis, as observed by nuclear as well as DNA fragmentation. Activation of caspase-3 and -9, but not caspase-8 or -12, was also demonstrated in vWD(m)-expressing cells. An inhibition of Akt phosphorylation, a major survival signaling component, also occurred in vWD(m)-expressing HeLa cells. Together these data suggest that vWD(m) induces apoptosis by inactivation of survival signaling component Akt and activation of caspase cascade (mitochondrial pathway) in HeLa cells. We propose SVS-1-vWD(m)as an alternative gene for use in developing new therapeutic strategies for the treatment of cancer.     

Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer

Recent discovery of mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in lung adenocarcinoma greatly stimulated biomarker research on predictive factors for EGFR tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib. Although patients with activating mutations of the EGFR generally respond to EGFR TKIs very well, it is natural to assume that there is no sole determinant, considering great complexity and redundancy of the EGFR pathway. Subsequently, roles of different types of EGFR mutations or mutations of genes that are members of the EGFR pathway such as KRAS and HER2 have been evaluated. In this review, we summarize the recent findings about how mutations of the EGFR and related genes affect sensitivity to EFGR-TKIs. We also discuss molecular mechanisms of acquired resistance to EGFR-TKIs that is almost inevitable in EGFR-TKI therapy. The door for genotype-based treatment of lung cancer is beginning to open, and through these efforts, it will be possible to slow the progression of lung cancer and eventually, to decrease mortality from lung cancer. ( Cancer Sci 2007; 98: 1817–1824)     

Interinstitutional variations in planning for stereotactic body radiation therapy for lung cancer

PURPOSE: The aim of this study was to assess interinstitutional variations in planning for stereotactic body radiation therapy (SBRT) for lung cancer before the start of the Japan Clinical Oncology Group (JCOG) 0403 trial. METHODS AND MATERIALS: Eleven institutions created virtual plans for four cases of solitary lung cancer. The created plans should satisfy the target definitions and the dose constraints for the JCOG 0403 protocol. RESULTS: FOCUS/XiO (CMS) was used in six institutions, Eclipse (Varian) in 3, Cadplan (Varian) in one, and Pinnacle3 (Philips/ADAC) in one. Dose calculation algorithms of Clarkson with effective path length correction and superposition were used in FOCUS/XiO; pencil beam convolution with Batho power law correction was used in Eclipse and Cadplan; and collapsed cone convolution superposition was used in Pinnacle3. For the target volumes, the overall coefficient of variation was 16.6%, and the interinstitutional variations were not significant. For maximal dose, minimal dose, D95, and the homogeneity index of the planning target volume, the interinstitutional variations were significant. The dose calculation algorithm was a significant factor in these variations. No violation of the dose constraints for the protocol was observed. CONCLUSION: There can be notable interinstitutional variations in planning for SBRT, including both interobserver variations in the estimate of target volumes as well as dose calculation effects related to the use of different dose calculation algorithms.     

Weekly paclitaxel therapy is curative for patients with retroperitoneal liposarcoma

In March 2004, we resected a giant retroperitoneal liposarcoma and the transverse colon, spleen and left kidney in a 58-year-old woman. In July, recurrence was detected in the right pelvis and left upper abdomen; therefore, we resected the tumor. In September 2004, computed tomography (CT) revealed multiple recurrences in the right lower abdomen, left upper abdomen, front of the left lobe of the liver, and at the back of the stomach. In October 2004, we started mesna, doxorubicin, ifosfamide, and dacarbazine therapy (MAID); however, after 1 course, the disease progressed, and the patient developed edema in the bilateral legs due to inferior vena cava (IVC) compression. In November 2004, we started weekly paclitaxel therapy (100 mg/m(2), once a week for 3 weeks followed by 1 drug-free week). CT revealed no change as a result of chemotherapy; however, IVC compression had improved, and leg edema had decreased. In August 2005, chemotherapy was stopped; therefore,the patient's condition worsened. She died in September 2005. We performed weekly paclitaxel therapy for the patient with recurrent liposarcoma. This improved her symptoms and quality of life (QOL). Therefore,we consider weekly paclitaxel therapy to be effective for liposarcoma treatment.     

A case successfully treated by desensitization for paclitaxel-associated hypersensitivity reactions

We report a case of a 56-year-old woman with hypersensitivity reactions (HSRs) symptoms against paclitaxel (PTX) which were suppressed by pre-injection of a low-dose of PTX before the full-dose injection. She received PTX chemotherapy (120 mg/body/week for three weeks on the 1st, 8th, and 15th day, followed by no drug for one week) in October 2004 for right breast cancer. However, continuation of the therapy was in jeopardy due to respiratory difficulties and facial flushing, considered to be HSRs symptoms, on day 15. However,we were able to continue the PTX chemotherapy by administering a low-dose pre-injection (2 mg/100 mL/30 min) before the full-dose injection. After that, HSRs symptoms were observed, but we were able to administer another low-dose pre-injection (1 mg/100 mL/30 min). Three courses of chemotherapy were successfully performed, followed by radical surgery in February 2005. A pathological complete response (pCR) of the maintumor was achieved. We suggest that pre-injection of a low-dose of PTX before the full-dose injection may be effective for prevention of the onset of HSRs symptoms.     

Irinotecan+cisplatin and irradiation are effective for brain metastases of gastric cancer--two case reports

We treated two patients in whom irinotecan (CPT-11)+cisplatin (CDDP) and irradiation showed efficacy against brain metastases of gastric cancer. CPT-11 and CDDP were administered on days 1 and 15 of a 28-day cycle at 60 mg/m(2) and 30 mg/m(2), respectively. The first patient was a 63-year-old man,who complained of headache and weakness. In March 2003, he was diagnosed as having Stage IV gastric cancer with peritoneal dissemination (T3, Nx, P1) and underwent total gastrectomy with D1 dissection. Chemotherapy with S-1 was continued after surgery. Two years and two months later, a metastatic tumor was found in the upper lobe of the right lung. The protocol was changed to S-1+CDDP, but progression of his disease occurred. The weekly paclitaxel (PTX) therapy was tried instead. Seven months later, he developed headache and weakness, and multiple brain metastases were diagnosed by CT scanning. We performed total brain irradiation (30 Gy) and started CPT-11+CDDP therapy, which was continued on a fortnightly basis at 60 mg/m(2) and 30 mg/m(2), respectively. The brain metastases regressed (PR), and this therapy led to a marked improvement in his quality of life. The second patient was a 78-year-old man, who complained of weakness of the lower extremities and dizziness. In November 2003, he was diagnosed as having stage IB gastric cancer (T2 (ss), N0, P0), and underwent total gastrectomy and splenectomy with D2 dissection. One year and four months later, local recurrence at the anastomosis was detected, as well as a metastatic tumor in the right lung. S-1, S-1+CDDP, and weekly PTX therapy were all tried. One year later, the patient was admitted with weakness and dizziness,and brain metastases were detected by CT scanning. We then performed Cyber Knife treatment and administered CPT-11+CDDP. As a result, his brain metastases partially regressed (PR).     

Assessment of health-related quality of life after radiofrequency ablation or laparoscopic surgery for small renal cell carcinoma: a prospective study with medical outcomes Study 36-Item Health Survey (SF-36)

OBJECTIVE: The purpose of this study was to assess the changes in health-related quality of life (HRQoL) during follow-up period in patients treated with percutaneous radiofrequency ablation (RFA) or laparoscopic surgery for small renal cell carcinoma. METHODS: From December 2004 through September 2006, for 37 consecutive patients, who were diagnosed with renal cell carcinoma and underwent percutaneous RFA (n = 20) or laparoscopic radical nephrectomy (n = 17) at our institution. HRQoL was evaluated prospectively using SF-36 Health survey pre- and post-operatively (1, 4, 12 and 24 weeks after surgery). RESULTS: Four of the eight scale scores of SF-36 were significantly lower pre-operatively in the RFA group than in the laparoscopic surgery group. The QoL scores in physical functioning, role-physical functioning and role-emotional functioning were significantly reduced one week after laparoscopic surgery. However, there was no reduction of the SF-36 QoL scores one week after operation in the RFA group. Furthermore, HRQoL scores in the RFA group showed a tendency to improve during follow-up periods. CONCLUSIONS: This is the first study to evaluate HRQoL changes (up to 24 weeks) in patients who have undergone RFA or laparoscopic radical nephrectomy for small renal cell carcinoma. No reduction, but rather an improvement, in HRQoL was seen in the RFA group during follow-up periods. From the point of view of QoL, RFA could be a viable alternative treatment for selected patients with small renal cell carcinoma. RFA could be a viable alternative treatment for the selected patients with small renal cell carcinoma.