The significance of scirrhous gastric cancer cell lines: the molecular characterization using cell lines and mouse models.

Scirrhous gastric cancer (SGC) exhibits aggressiveness of the rapid infiltrating tumor cells with abundant fibroblasts. Experimental studies using SGC cell lines have obtained useful information about this cancer. Our literature search divulged a total of 18 SGC cell lines; two cell lines were established from primary SGC and the other lines were established from a metastatic lesion of SGC. Fibroblast growth factor receptor 2 (FGFR2) and transforming growth factor-beta receptor (TßR) are linked to the rapid development of SGC. Cross-talk between the cancer cells and cancer-associated fibroblasts (CAFs) has been shown to contribute to the progression of SGC. Chemokine (C-X-C motif) receptor 1 (CXCR1) from SGC cells might be associated with the abundant CAFs in cancer microenvironments. The in vivo models established using SGC cell lines are expected to serve as a useful tool for the development of drugs such as FGFR2 inhibitors, TßR inhibitors, and CXCR1 inhibitors, which might be promising as SGC treatments. However, the number of available SGC cell lines is insufficient for the clarification of the entire biologic behavior of SGC. Since the mechanisms responsible for the characteristic aggressiveness of SGC are not fully elucidated, the establishment of new SGC cell lines could help clarify the biological behavior of SGC and contribute to its treatment.

Prognostic value of extracapsular invasion of axillary lymph nodes combined with peritumoral vascular invasion in patients with breast cancer.

BACKGROUND: Extracapsular invasion (ECI) of metastatic axillary lymph nodes has been associated with aggressive nodal disease but its prognostic role in breast cancer is unclear. The present study evaluated nodal ECI as a predictor of breast cancer recurrence. METHODS: We evaluated 154 women with histologically proven node-positive breast cancer who were diagnosed with invasive ductal carcinoma, and investigated the relationships between ECI and recurrences and other clinicopathological factors, particularly vascular invasion and the number of lymph node metastases. RESULTS: The presence of ECI at positive nodes was significantly associated with the number of positive nodes, and with disease recurrence and survival in univariate (but not multivariate) analysis. Interestingly, all ECI(+) patients with distant metastases in our series had peritumoral vascular invasion (PVI), which may have reflected systemic disease; ECI with PVI of the primary tumor strongly predicted recurrent disease and shorter survival. CONCLUSION: ECI of axillary metastases combined with PVI indicates high tumor aggressiveness. Patients with ECI and PVI may be considered for stronger adjuvant therapies because of their high risk for distant recurrences.

[The case of a long-surviving patient with breast cancer and brain metastases treated using multidisciplinary therapy].

We present the case of a 55-year-old-woman who was diagnosed with left breast cancer, and underwent a left mastectomy and left axillary lymph node resection. The histopathological examination indicated scirrhous carcinoma and lesser papillotubular carcinoma[estrogen receptor-negative (ER-), progesterone receptor-negative(PgR-), and human epidermal growth factor receptor 2-positive, grade 3 (HER2, 3+)] with lymph node metastases. Adjuvant chemotherapy consisting of epirubicin and cyclophosphamide (EC) followed by paclitaxel was administered. During the therapy, the patient noticed a mass on her left chest wall. It was diagnosed as a locally recurrent tumor. A computed tomography (CT) scan indicated supraclavicular lymph node metastasis. The patient underwent radiotherapy and was administered chemotherapy with TS-1 and trastuzumab. Brain metastases were found 24 months postoperatively, and the patient underwent surgery and wholebrain radiotherapy. After these, systemic capecitabine and trastuzumab chemotherapy was administered. The therapy was subsequently changed to capecitabine and lapatinib. There have been no subsequent metastatic tumors, and good control has been achieved for a long time after the detection of brain metastases.

A patient with scirrhous stomach cancer treated with combination of hyperthermotherapy and 5-aminolevulinic acid (ALA).

A 35-year-old female with scirrhous stomach cancer (stage IV) was treated with a combination of 5-aminolevulinic acid (ALA), sodium dichloroacetate (DCA), hyperthermotherapy, and immunotherapy as terminal care. The patient survived for one year and seven months, during which her quality of life was markedly improved and she returned to work. The patient was diagnosed with poorly-differentiated adenocarcinoma and progressive signet-ring cell carcinoma, accompanied by left ovarian metastasis, peritoneal dissemination, and right hydronephrosis stage IV, and treated with combination chemotherapy with tegafur-gimeracil-oteracil potassium (TS-1) and docetaxel. Oral ALA and DCA were concomitantly administered at 50 mg each three times a day (150 mg/day, respectively). In addition, hyperthermotherapy using thermotron was concomitantly performed at 2- to 3-week intervals. Cellular immunotherapy with αß T- and immature dendritic cells was also performed. The disease did not progress for 11 months, her quality of life was markedly improved, and she was able to return to work. However, the signs of enlargement of the ovarian metastatic lesion were noted later, for which chemotherapy with four cycles of second-line paclitaxel and a half dose of irinotecan and cisplatin as third-line treatment were performed. Combination of ALA/DCA, hyperthermotherapy, and cellular immunotherapy may be a low-invasive palliative therapy superior in maintaining quality of life of tumor-bearing terminally ill individuals.

Intraperitoneal delivery of a small interfering RNA targeting NEDD1 prolongs the survival of scirrhous gastric cancer model mice.

The prognosis of patients with advanced diffuse-type gastric cancer (GC), especially scirrhous gastric cancer (SGC) remains extremely poor. Peritoneal carcinomatosis is a frequent form of metastasis of SGC. With survival rates of patients with peritoneal metastasis at 3 and 5 years being only 9.8% and 0%, respectively, development of a new treatment is urgently crucial. For such development, the establishment of a therapeutic mouse model is required. Among the 11 GC cell lines we examined, HSC-60 showed the most well-preserved expression profiles of the Hedgehog and epithelial-mesenchymal transition pathways found in primary SGCs. After six cycles of harvest of ascitic tumor cells and their orthotopic inoculation in scid mice, a highly metastatic subclone of HSC-60, 60As6 was obtained, by means of which we successfully developed peritoneal metastasis model mice. The mice treated with small interfering (si) RNA targeting NEDD1, which encodes a gamma-tubulin ring complex-binding protein, by the atelocollagen-mediated delivery system showed a significantly prolonged survival. Our mouse model could thus be useful for the development of a new therapeutic modality. Intraperitoneal administration of siRNAs of targeted genes such as NEDD1 could provide a new opportunity in the treatment of the peritoneal metastasis of SGC.

Usefulness of multidisciplinary therapy combining neoadjuvant chemotherapy with S-1 plus cisplatin and postoperative sequential chemotherapy in patients with scirrhous gastric cancer.

BACKGROUND/AIMS: The outcomes of patients with scirrhous gastric cancer (SGC) remain poor. We retrospectively compared outcomes according to historically different treatments for SGC and studied the therapeutic usefulness of NAC with S-1 plus cisplatin followed by postoperative sequential chemotherapy. METHODOLOGY: We studied 93 patients with SGC. Between 1995 and 2000, 29 patients did not receive NAC and were instead given conventional anti-cancer drugs. Between 2000 and 2003, 20 patients received 4 weeks of NAC with low-dose cisplatin plus 5-fluorouracil (5-FU) followed by postoperative sequential treatment with new anticancer agents (neoadjuvant low-dose FP group). Between 2003 and 2006, 44 patients received 2 courses of NAC with S-1+cisplatin followed by postoperative sequential administration of new anticancer agents (neoadjuvant S-1+cisplatin group). Response rates and overall survival were compared among the treatment groups. RESULTS: The rates of response to NAC were 15% in the neoadjuvant low-dose FP group and 36% in the neoadjuvant S-1+cisplatin group. Overall survival was significantly longer in the neoadjuvant S-1+cisplatin group than the other groups. CONCLUSIONS: Our results suggest that multidisciplinary therapy combining NAC with S-1+cisplatin and postoperative sequential administration of new anticancer drugs is therapeutically useful in patients with SGC.

Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma.

Expression levels of the novel tumor suppressor gene REIC/Dkk-3 are reduced in many human cancers. We have previously showed that an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) induced apoptosis of cancer cells selectively and exerted bystander antitumor effects via ER stress. We examined possible effects of Ad-REIC in a peritoneal dissemination model of scirrhous gastric carcinoma (SGC). Among various types of gastric cancer, SGC continues to be associated with the worst prognosis due to a high incidence of metastases in the peritoneal cavity. We found that a single intraperitoneal injection of Ad-REIC suppressed tumor dissemination and disease progression. Immunomodulation by Ad-REIC led to recruitment of natural killer cells inside tumor nodules. We conclude that Ad-REIC gene therapy may be a potential tool in combinatorial approaches to achieve curative effects in SGC.

The metastasis-associated microRNA miR-516a-3p is a novel therapeutic target for inhibiting peritoneal dissemination of human scirrhous gastric cancer.

Although aberrant microRNA (miRNA) is expressed in different types of human cancer tissues, its pathophysiologic role and the relevance of tumorigenesis and metastasis are still largely unknown. Here, we defined miRNAs involved in cancer metastasis (metastamirs) using an established mouse model for peritoneal dissemination of human scirrhous gastric carcinoma cells. Highly metastatic derivatives (44As3 cells) were derived from the parental cells originally isolated from patients (HSC-44PE cells). Using microarray analysis to identify differentially expressed miRNAs in 44As3 and HSC-44PE cells, we focused on miR-516a-3p as a candidate antimetastatic miRNA (antimetastamir) whose functions in cancer had not been studied. We confirmed attenuated expression of miR-516a-3p in 44As3 cells compared with HSC-44PE cells by Northern blot analysis and quantitative reverse transcriptase PCR. Stable ectopic overexpression in 44As3-miR-516a-3p cells permitted identification of sulfatase 1 as a direct target of the miRNA, through use of the isobaric tagging reagent iTRAQ and the QSTAR Elite Hybrid LC-MS/MS system. Sulfatase 1 is known to remove 6-O-sulfates from heparan sulfate proteoglycans on the cell surface, causing release of membrane-bound Wnt ligands from cells. Consistent with this function, Western blot analyses revealed high levels of Wnt3a, Wnt5a, and nuclear ß-catenin accumulation in 44As3 cells but relatively reduced levels in 44As3-miR-516a-3p cells. Notably, orthotopic inoculation of nude mice with 44As3-miR-516a-3p cells yielded significantly longer survival periods compared with mice inoculated with control 44As3 cells. Through atelocollagen-mediated delivery of an miR-516a-3p expression vector into orthotopic 44As3 tumors, we documented its feasibility as a treatment agent. Our findings define the miRNA miR-516-3p as an antimetastamir with potential therapeutic applications in blocking metastatic dissemination of gastric cancers.

[A case of type 4 gastric cancer with positive peritoneal lavage cytology, which relapsed at the peritoneum at the time of seven years and eight months after resection].

A 55-year-old woman was admitted to our hospital with a complaint of appetite loss and body weight loss. Upper digestive endoscopy showed a giant fold at the greater curvature stomach and diffused edematous gastric mucosa. Abdominal contrast CT demonstrated a significant thickening of the gastric wall and a large number of lymph node swelling. A clinical finding was Stage IIIB (T3N2M0) Type 4 gastric cancer of poorly differentiated adenocarcinoma. Total gastrectomy, splenectomy and D2 lymph node dissection were performed. Although there was no peritoneal dissemination, peritoneal lavage cytology was positive. After the operation, S-1 alone chemotherapy was administered for four years. No recurrence had occurred for about seven years and eight months after resection. However, the patient was pointed out the signs of recurrence (ascites and induration) by CT. Now, S-1 alone chemotherapy was performed again, and the patient has been in good health.

[Three scirrhous gastric cancer cases with CY negativity in second-look staging laparoscopy after chemotherapy to whom curative surgery was carried out].

Case 1: A 77-year-old female with scirrhous gastric cancer was diagnosed as c4T3N1H0M0P0CY1/stage IV, and S-1/docetaxel combined therapy was carried out. The wall thickness of stomach improved after 11 courses. Case 2: A 48-year-old female with scirrhous gastric cancer was diagnosed as c4T3N1H0M0P0CY1/stage IV, and S-1/CDDP/paclitaxel combined therapy was carried out. The wall thickness of stomach improved after 5 courses. Case 3: A 37-year-old man with scirrhous gastric cancer was diagnosed as c4T3N0H0M0P1CY1/stage IV, and S-1/CDDP/paclitaxel combined therapy was carried out. The wall thickness of stomach improved after 5 courses. In all cases, CY and P negativity was confirmed in second-look staging laparoscopy and curative surgery was carried out.

Retrospective analysis of prognosis for scirrhous-type gastric cancer: one institution's experience.

BACKGROUND: Scirrhous gastric cancer is biologically aggressive, and the prognosis is poor even with curative surgery. We compared outcomes with different therapies in order to identify prognostic factors. METHODS: Records for 83 patients, who were treated between 1991 and 2004, were evaluated for survival and stage, treatment, and clinicopathological factors. RESULTS: Cumulative 5-year overall survival was 10.2% for all 83 patients, including 27 (32.5%) patients with stage II/III disease and 56 (67.4%) with stage IV disease. The 5-year overall survival rate and median survival time for patients with stage II/III disease after curative surgery were 24.3% and 1150 days. For patients with stage IV disease, 2-year and 5-year survival rates after initial surgery were 13.7% and 0% and median survival was 250 days. In contrast, preoperative chemotherapy for advanced, unresectable disease produced 2-year and 3-year overall survival rates of 53.6% and 26.8% and medican survival was 910 days. CONCLUSION: Aggressive surgery alone does not seem to improve outcome, but preoperative chemotherapy might be beneficial and should be investigated further.

Flare-up of dermatomyositis along with recurrence of breast cancer.

Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations. The association between dermatomyositis and malignancy is becoming more clearly delineated. A sort of dermatomyositis is thought to be paraneoplastic syndrome and dermatomyositis may follow clinical course of malignancy. We report a 68-year-old woman with dermatomyositis, whose clinical onset of dermatomyositis was apparently concomitant with breast cancer. Dermatomyositis had settled down and oral steroid could be tapered after the resection of breast cancer. Creatine kinase value was elevated before the detection of the first and second recurrence and in the terminal state. At the second recurrence, skin lesions and creatine kinase value had flared up and immediate metastatic check-up revealed the recurrence. Our case shows dermatomyositis, which was thought to be paraneoplastic syndrome, that followed clinical course of malignancy and suggests immediate check-up is needed for early detection of recurrence when dermatomyositis flares up after the resection of the malignancy.

Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib (ZD1839, Iressa) for disseminated peritoneal scirrhous gastric cancer.

We evaluated the effect of a "tailor-made" chemo-gene therapy in scirrhous gastric cancer (SGC)-bearing nude mice. For this tailor-made approach, we first selected gefitinib (epidermal growth factor receptor-tyrosine kinase inhibitor)-sensitive SGC cell lines, and 5/8 cell lines demonstrated various degrees of gefitinib-sensitivity. In the highly gefitinib-sensitive NUGC-4, the biological response to NK4 (HGF antagonist/angiogenesis inhibitor) was examined. Subsequently, the composition of an NK4-expressing ternary complex (cationic lipid/nucleic acid/HMG-1, 2 protein) was optimized for maximum transfection activity in NUGC-4. Finally, mice were peritoneally coinoculated with NUGC-4 and scirrhous-associated gastric fibroblasts, NF22, on day 0. Animal models were orally administrated gefitinib (50 mg/kg/day, on days 7-28), and peritoneally NK4-expressing ternary complex (on days 14, 21 and 28). NK4-expression suppressed the gefitinib-resistance induced by the interaction between fibroblasts and SGC, and eventually, this tailor-made combination synergistically decelerated the disease progression by inhibiting proliferative, angiogenic and antiapoptotic effects in tumor tissues. On day 28, both the hemoglobin concentration (g/dl) (control (n = 8), 11.9; treated (n = 8), 17.3; p = 0.0014) and the numbers of mice in good condition (control, 2; treated, 8; p = 0.0012) were significantly greater, and the abdominal girth (mm) (control, 81.1; treated, 70.3; p = 0.0036) was significantly reduced. The median points of bloody ascite-free survival time (days) (control, 22; treated, 44; p < 0.0001) and time to euthanasia (days) (control, 36.5; treated, 56; p < 0.0001) were also significantly prolonged. This combination is a potentially useful approach to the treatment of peritoneal gefitinib-sensitive SGC dissemination.

Therapeutic strategy for scirrhous type gastric cancer.

BACKGROUND/AIMS: As no appropriate therapeutic strategy has yet been established in scirrhous type gastric cancer, we retrospectively analyzed the therapeutic outcomes in patients with this type of cancer. METHODOLOGY: A total of 183 patients with scirrhous type gastric cancer were enrolled in the study. 127 of them underwent resection; 61 potentially curative gastrectomy; 66 palliative resection; and 56 had no surgery. RESULTS: Univariate analysis revealed that the number of metastatic lymph nodes and the depth of invasion influenced prognosis in curatively resected cases, whereas no factor did so after palliative resection. Multivariate analysis showed that prognosis was affected independently by peritoneal metastasis and non-regional lymph node metastasis in all resected cases, but by the number of metastatic lymph nodes in curatively resected cases. There was no significant difference in survival between patients undergoing and those not undergoing palliative gastrectomy. Prophylactic (6) and therapeutic CHPP (12) had no efficacy on peritoneal metastasis. Furthermore, left upper abdominal evisceration (LUAE) (9) did not improve long-term results in curatively resected cases. CONCLUSIONS: In scirrhous type gastric cancer, gastrectomy including extended lymph node dissection is justified only in patients with limited lymph node metastasis, and palliative gastrectomy should be not performed because it has no efficacy on survival.

Management protocol for scirrhous gastric cancer.

BACKGROUND: The prognosis for patients with scirrhous gastric cancer (SGC) is extremely poor. However, the management protocol for this type of cancer has not been well discussed. In this study, we retrospectively evaluated the management of SGC and we introduced a new treatment protocol for SGC. PATIENTS AND METHODS: Between 1991 and 2001, 58 patients with SGC were treated. Thirty-nine, who underwent gastrectomy, were divided into 3 sub-groups according to peritoneal metastasis (P) and peritoneal washing cytology (CY) status [P(-)/CY(-), P(-)/CY(+), and P(+)/CY(+)]. The survival rates of these 3 sub-groups were compared with patients who did not have a gastrectomy (n=19), retrospectively. From 2002, we started a new treatment protocol for SGC. Laparoscopic diagnosis of P or CY and intraperitoneal chemotherapy (IPC) were performed before performing laparotomy on 10 patients with SGC. RESULTS: The 5-year survival rate of the 19 patients in P(-)/CY(-) was 11.6%. The survival rates of patients with P(-)/CY(+) or patients with P(+)/CY(+) were no different from patients who did not have gastrectomy (pleural effusion or ascites negative). In 10 patients who were treated with the new protocol, 7 with P(-)/CY(-) underwent gastrectomy after IPC and 3 with P(+)/CY(+) underwent repeated IPC. CONCLUSION: Gastrectomy may not have prognostic benefit for patients with SGC with CY(+). Thus, we recommend laparoscopic diagnosis of peritoneal metastasis or peritoneal cytology before performing laparotomy on these patients.

Poorly differentiated carcinomas of the thyroid with trabecular, insular, and solid patterns: a clinicopathologic study of 183 patients.

BACKGROUND: The term poorly differentiated (PD) carcinoma was proposed 20 years ago to define aggressive, follicular-derived thyroid carcinomas with behavior intermediate between follicular/papillary and anaplastic carcinomas. Among the variable histologic patterns recognized in such tumors, trabecular-insular-solid (TIS) areas usually are predominant. Conversely, some authors pointed out that PD carcinomas are characterized by unequivocal, high-grade histology with atypias, high mitotic counts, and necrosis rather than by a specific growth pattern. METHODS: The clinicopathologic features of a series of 183 thyroid carcinomas with predominant (n = 165 tumors) or focal (n = 18 tumors) TIS growth patterns were studied by univariate and multivariate overall survival analyses and were compared with clinical outcomes. Subgroups included tumors with predominant oxyphilic features (n = 66 tumors) and (residual) papillary carcinoma features (n = 24 tumors). Control groups of papillary (n = 68 tumors), follicular (n = 71 tumors), and anaplastic (n = 35 tumors) carcinomas also were included for overall survival analysis. RESULTS: TIS carcinomas had an intermediate behavior between papillary/follicular and anaplastic carcinomas (P < 0.0001). Univariate and multivariate statistical analyses demonstrated that age > 45 years (P = 0.007), the presence of necrosis (P < 0.0001), and a mitotic count > 3 per 10 high-power fields (P = 0.01) were associated with poor outcome. A simplified scoring system based on statistically significant parameters allowed the identification of three prognostic subgroups (P < 0.0001). CONCLUSIONS: PD TIS carcinomas overall followed a more aggressive course compared with differentiated thyroid carcinomas, irrespective of the extent of the TIS component. However, a numeric scoring system applied to specific clinicopathologic parameters further may identify three prognostic categories of patients who have significantly different survival rates at 5 years and 10 years.

Neoadjuvant chemotherapy with S-1 for scirrhous gastric cancer: a pilot study.

We conducted a pilot study using S-1 (TS-1), a novel oral derivative of 5-fluorouracil, as neoadjuvant chemotherapy for potentially resectable scirrhous gastric cancer. The neoadjuvant chemotherapy consisted of two courses (each, 4-week administration and 2-week withdrawal) of S-1 at 100-120 mg/body per day. Five patients were enrolled in this pilot study and underwent resection. The response rate for the neoadjuvant chemotherapy was 60% (three partial response [PR]; two stable disease [SD]). Three of the five patients received curative resection; the other two patients received noncurative resection because of localized peritoneal dissemination and positive results on cytological examination of the abdominal washing. No toxicity of grade 3 or more was exhibited during the two courses of chemotherapy. Pathological examination of the resected specimens revealed a marked reduction in the distribution of viable cancer cells in the stomach in the three patients with PR. In one of these patients, pathological findings suggestive of the possibility of disappearance of the cancer cells in the perigastric and paraaortic lymph nodes were noted. Because of the unexpectedly high response to S-1, we consider that the efficacy of S-1 as neoadjuvant chemotherapy for scirrhous gastric cancer should be verified by phase II and III trials.

Predictive value of estrogen receptor status as assessed by ligand-binding assay in patients with early-stage breast cancer treated with breast conserving surgery and radiation therapy.

It is important to determine which factors are predictive for the prognosis of patients treated with breast conserving surgery (BCS) and radiation therapy (RT) in order to make a decision as to the adjuvant treatment. Although estrogen receptor (ER) is known to be a predictive marker for antiestrogens in breast cancer, the prognostic effect of hormone receptors has not been fully analyzed in Japanese breast cancer patients treated with BCS and RT. A total of 153 breast cancer patients having up to three positive nodes in the axilla as identified histologically and treated with both BCS and RT with or without systemic therapy were enrolled in this study. All tumors were measured for ER and progesterone receptor (PR) using ligand-binding assay (LBA). ER was inversely related to patients' age, however, PR was not related to any clinical features. When ER was classified into negative, weakly positive and strongly positive categories, with cut-off levels of zero and 50 fmol/mg protein, the relapse-free survival (RFS) was significantly better in patients with tumors having strongly positive ER than in patients with tumors having negative ER. Multivariate analysis revealed that ER as well as nodal status, was an independent predictive factor for RFS, however, PR was not. As a result, we believe that ER measured by LBA is valuable for predicting prognosis of early-stage breast cancer patients treated with BCS and RT.

A case report of immunotherapy on a patient with advanced gastric cancer by adoptive transfer of OK-432-reactive HLA-matched allogeneic lymphocytes.

Adoptive immunotherapy (AIT) for non-hematological malignancies, using HLA-matched donor lymphocytes, has been rarely reported. For a 35-year-old male patient with peritoneal disseminated advanced gastric cancer, we performed AIT using lymphocytes from his HLA-matched 37-year-old brother and a streptococcal preparation, OK-432, as an antigen. After the donor had been immunized by intradermal administration of OK-432, OK-432-reactive lymphocytes were induced in vitro and transferred to the patient intravenously with OK-432. Low-dose systemic immunochemotherapy, using interleukin-2, 5-fluorouracil and cyclophosphamide, was concurrently administered with AIT. As a result, the Schnitzler metastasis in the patient reduced in size without any significant graft-versus-host-related complications. One of the effector mechanisms of therapeutic benefit was suggested to be cytokine release from the transferred OK-432-reactive lymphocytes. Our findings suggest the safety and efficacy of AIT using lymphocytes from an HLA-matched sibling and OK-432 as an antigen. Further studies to investigate the use of tumor-associated antigen and an HLA-matched sibling's lymphocytes for AIT of advanced cancer are warranted.

[Osteogenesis imperfecta and breast carcinoma. A case study of radiobiological interest]. / Osteogenesis imperfecta und Mammakarzinom. Eine Fallstudie von radiobiologischem Interesse.

PURPOSE: Osteogenesis imperfecta (OI) is an inherited disorder of connective tissue with abnormal quality and/or quantity of type 1 collagen. The frequency of the association of OI and breast cancer as well as the frequency of radiation induced side-effects in patients with OI are not known. Certain diseases with widespread collagen alterations such as systemic lupus erythematodes or dermatomyositis--although not exactly comparable to congenital OI--carry a high risk for radiation injuries in case of irradiation with normal doses. The report of a patient with osteogenesis imperfecta type I and postmastectomy irradiation might therefore be of some radiobiological interest. METHODS: Report of a 46-year-old women with OI type I and breast cancer with a 14-year follow-up time after mastectomy and external beam irradiation. RESULTS: During all the follow-up time there was no radiation injury in this patient with OI type I and breast cancer. CONCLUSION: Mostly it is not possible to draw a valid conclusion from a case report, but with this experience the combination of OI type I and radiotherapy seems not to cause unusual radiation injury. Contrary to OI of type II and III, in the majority of the cases of OI type I there is a normal quality, but diminished quantity of collagen type I. This could be one of the possible reasons for the absence of adverse radiation effects. Finally, it might be of interest, that the gene-locus of the two alpha-1(I)-chains of collagen type I is situated at chromosome 17q21-22, where also the location of the "breast-cancer gene" is supposed to be. A genetic examination was, unfortunately, refused by the patient.