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95-490: HWI scientists work to find the fundamental causes of many diseases. For example, cancer is being attacked by identifying new classes of anti-tumor agents including new inhibitors for hormone -dependent breast tumors . Other projects include: HWI scientists use a methodology known as structural biology , which allows them to create 3D models of the molecules that build up cells. The investigation results provide many insights into how these molecular machines work, including

190-480: A glycopeptide isolated from Streptomyces verticillus , also intercalates DNA, but produces free radicals that damage DNA. This occurs when bleomycin binds to a metal ion , becomes chemically reduced and reacts with oxygen . Mitomycin is a cytotoxic antibiotic with the ability to alkylate DNA. Most chemotherapy is delivered intravenously , although a number of agents can be administered orally (e.g., melphalan , busulfan , capecitabine ). According to

285-541: A mutual savings bank , founded by Samuel H. Mather. In 1867, the modest but growing bank built Cleveland 's first skyscraper , the 10-story Society for Savings Building on Public Square . Despite erecting the tallest structure between New York and Chicago at the time, the bank largely eschewed expansion. That aspect is highlighted by the fact that when it celebrated its 100th anniversary in 1949, it still only had one office although it had over $ 200 million (~$ 2.03 billion in 2023) in deposits. This conservatism helped

380-459: A nucleobase , a sugar and a phosphate group . The nucleobases are divided into purines ( guanine and adenine ) and pyrimidines ( cytosine , thymine and uracil ). Anti-metabolites resemble either nucleobases or nucleosides (a nucleotide without the phosphate group), but have altered chemical groups . These drugs exert their effect by either blocking the enzymes required for DNA synthesis or becoming incorporated into DNA or RNA. By inhibiting

475-521: A 947-foot skyscraper that was more commensurate with a major bank headquarters than the modest buildings used in Albany. These issues made Cleveland the preferable location for the merged bank's headquarters. Conversely, Key's brand was more recognizable. The deal was structured as a merger of equals. The merged bank took the KeyCorp name, and operates under the charter of the old KeyCorp. However, Society

570-660: A bill chartering the Commercial Bank of Albany. In 1865, Commercial Bank was reorganized under the National Banking Act of 1864, and changed its name to National Commercial Bank of Albany. Over a hundred years passed before National Commercial merged with First Trust and Deposit of Syracuse to become First Commercial Banks in 1971, still a modest New York State bank with 89 offices. Victor J. Riley Jr. became president and CEO in 1973, and changed First Commercial's name to Key Bank Inc. in 1979. Riley embarked on

665-414: A certain dose, the effect plateaus and proportionally no more cell death occurs with increased doses. Subtypes of the anti-metabolites are the anti-folates , fluoropyrimidines, deoxynucleoside analogues and thiopurines . The anti-folates include methotrexate and pemetrexed . Methotrexate inhibits dihydrofolate reductase (DHFR), an enzyme that regenerates tetrahydrofolate from dihydrofolate . When

760-526: A community bank. By 1993, the rural strategy with local management and minimal technology made Key a very profitable bank. However, it was getting tougher for Riley and CFO William Dougherty to maintain their 15% return on equity target and investors were cooling on Key stock after many high growth years. Key began testing a Vision 2001 computer system, which sped up and enhanced the loan process through faster credit scoring, loan servicing, and collection capabilities. Although Gillespie had built Society into

855-598: A founding member of the Buffalo Medical Group. One of his patients, Helen Woodward Rivas, expressed great interest in funding a medical research effort in Buffalo. Through her $ 3 million (equivalent to $ 33,621,000 in 2023) gift, the Medical Foundation (MFB) came into being. An example of the basic research carried out includes studying disease processes at the molecular scale. For example it

950-444: A high index of suspicion and the use of CT scanning, nonoperative treatment for uncomplicated cases, and sometimes elective right hemicolectomy to prevent recurrence. Nausea , vomiting , anorexia , diarrhea , abdominal cramps, and constipation are common side-effects of chemotherapeutic medications that kill fast-dividing cells. Malnutrition and dehydration can result when the recipient does not eat or drink enough, or when

1045-546: A large extent, chemotherapy can be thought of as a way to damage or stress cells, which may then lead to cell death if apoptosis is initiated. Many of the side effects of chemotherapy can be traced to damage to normal cells that divide rapidly and are thus sensitive to anti-mitotic drugs: cells in the bone marrow , digestive tract and hair follicles . This results in the most common side-effects of chemotherapy: myelosuppression (decreased production of blood cells, hence that also immunosuppression ), mucositis (inflammation of

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1140-417: A number of strategies in the administration of chemotherapeutic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms . All chemotherapy regimens require that the recipient be capable of undergoing the treatment. Performance status is often used as a measure to determine whether a person can receive chemotherapy, or whether dose reduction

1235-611: A plan to grow Key through acquisitions. From the mid-1970s to the early 1980s, it made numerous acquisitions throughout upstate New York . Beginning in the 1980s, Riley looked outside New York, expanding Key's footprint with an acquisition in Maine , and eventually adding branches in Massachusetts and Vermont . However, by the mid-1980s, banking regulators in New England began looking askance at New York-based banks controlling

1330-767: A preventative and treatment effect of diarrhoea related to chemotherapy alone and with radiotherapy. However, a high index of suspicion is appropriate, since diarrhoea and bloating are also symptoms of typhlitis , a very serious and potentially life-threatening medical emergency that requires immediate treatment. Anemia can be a combined outcome caused by myelosuppressive chemotherapy, and possible cancer-related causes such as bleeding , blood cell destruction ( hemolysis ), hereditary disease, kidney dysfunction, nutritional deficiencies or anemia of chronic disease . Treatments to mitigate anemia include hormones to boost blood production ( erythropoietin ), iron supplements , and blood transfusions . Myelosuppressive therapy can cause

1425-601: A recent (2016) systematic review, oral therapies present additional challenges for patients and care teams to maintain and support adherence to treatment plans. There are many intravenous methods of drug delivery, known as vascular access devices. These include the winged infusion device , peripheral venous catheter , midline catheter, peripherally inserted central catheter (PICC), central venous catheter and implantable port . The devices have different applications regarding duration of chemotherapy treatment, method of delivery and types of chemotherapeutic agent. Depending on

1520-469: A regional powerhouse in the Midwest , he wanted to vault the bank into the big leagues. He concluded Key, a bank with similar ambitions, was a suitable partner. Society and Key held talks in 1990 at Gillespie's prompting, but Riley decided to stay the course of smaller, more lucrative acquisitions with obvious synergies. Yet, news reports swirled that a possible merger was in the works in the fall of 1993. Key

1615-416: A standard regimen . Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim only to prolong life or to reduce symptoms ( palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer , which is called medical oncology . The term chemotherapy now means

1710-401: A state of assembly and disassembly. Vinca alkaloids and taxanes are the two main groups of anti-microtubule agents, and although both of these groups of drugs cause microtubule dysfunction, their mechanisms of action are completely opposite: Vinca alkaloids prevent the assembly of microtubules, whereas taxanes prevent their disassembly. By doing so, they can induce mitotic catastrophe in

1805-496: A tendency to bleed easily, leading to anemia. Medications that kill rapidly dividing cells or blood cells can reduce the number of platelets in the blood, which can result in bruises and bleeding . Extremely low platelet counts may be temporarily boosted through platelet transfusions and new drugs to increase platelet counts during chemotherapy are being developed. Sometimes, chemotherapy treatments are postponed to allow platelet counts to recover. KeyBank KeyBank

1900-484: Is systemic therapy for cancer: they are introduced into the blood stream (the system) and therefore can treat cancer anywhere in the body. Systemic therapy is often used with other, local therapy (treatments that work only where they are applied), such as radiation , surgery , and hyperthermia . Traditional chemotherapeutic agents are cytotoxic by means of interfering with cell division (mitosis) but cancer cells vary widely in their susceptibility to these agents. To

1995-479: Is a "life-threatening gastrointestinal complication of chemotherapy." Typhlitis is an intestinal infection which may manifest itself through symptoms including nausea , vomiting , diarrhea , a distended abdomen , fever , chills , or abdominal pain and tenderness. Typhlitis is a medical emergency . It has a very poor prognosis and is often fatal unless promptly recognized and aggressively treated. Successful treatment hinges on early diagnosis provided by

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2090-1054: Is a nucleobase analogue that is metabolised in cells to form at least two active products; 5-fluourouridine monophosphate (FUMP) and 5-fluoro-2'-deoxyuridine 5'-phosphate (fdUMP). FUMP becomes incorporated into RNA and fdUMP inhibits the enzyme thymidylate synthase; both of which lead to cell death. Capecitabine is a prodrug of 5-fluorouracil that is broken down in cells to produce the active drug. The deoxynucleoside analogues include cytarabine , gemcitabine , decitabine , azacitidine , fludarabine , nelarabine , cladribine , clofarabine , and pentostatin . The thiopurines include thioguanine and mercaptopurine . Anti-microtubule agents are plant -derived chemicals that block cell division by preventing microtubule function. Microtubules are an important cellular structure composed of two proteins, α-tubulin and β-tubulin . They are hollow, rod-shaped structures that are required for cell division, among other cellular functions. Microtubules are dynamic structures, which means that they are permanently in

2185-700: Is an American regional bank headquartered in Cleveland, Ohio , and the 25th largest bank in the United States. Organized under the publicly traded KeyCorp , KeyBank was formed from the 1994 merger of the Cleveland-based Society Corporation, which operated Society National Bank, and the Albany-headquartered KeyCorp. The company today operates over 1,000 branches and 40,000 ATMs, mostly concentrated in

2280-568: Is an important factor in achieving better treatment outcomes. Similar results were found in a study involving people with colorectal cancer who have been treated with the popular FOLFOX regimen. The incidence of serious diarrhea was reduced from 12% in the BSA-dosed group of patients to 1.7% in the dose-adjusted group, and the incidence of severe mucositis was reduced from 15% to 0.8%. The FOLFOX study also demonstrated an improvement in treatment outcomes. Positive response increased from 46% in

2375-500: Is an independent prognostic predictor of survival in various cancer types. Alkylating agents are the oldest group of chemotherapeutics in use today. Originally derived from mustard gas used in World War I , there are now many types of alkylating agents in use. They are so named because of their ability to alkylate many molecules, including proteins , RNA and DNA . This ability to bind covalently to DNA via their alkyl group

2470-494: Is coupled with quality wines and champagne and the influence of the shape of the glass on the taste demonstrated. The link between the glass, wine and research, comes from the use of crystals in the research and the rich information they supply when examined in detail. Anti-tumor Chemotherapy (often abbreviated chemo , sometimes CTX and CTx ) is the type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents ) in

2565-536: Is obtained from the Chinese ornamental tree Camptotheca acuminata . Drugs that target topoisomerase II can be divided into two groups. The topoisomerase II poisons cause increased levels enzymes bound to DNA. This prevents DNA replication and transcription, causes DNA strand breaks, and leads to programmed cell death ( apoptosis ). These agents include etoposide , doxorubicin , mitoxantrone and teniposide . The second group, catalytic inhibitors, are drugs that block

2660-668: Is required. Because only a fraction of the cells in a tumor die with each treatment ( fractional kill ), repeated doses must be administered to continue to reduce the size of the tumor. Current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity. The effectiveness of chemotherapy depends on the type of cancer and the stage. The overall effectiveness ranges from being curative for some cancers, such as some leukemias , to being ineffective, such as in some brain tumors , to being needless in others, like most non-melanoma skin cancers . Dosage of chemotherapy can be difficult: If

2755-493: Is similar to that of vinca alkaloids in that they bind to tubulin, inhibiting microtubule formation. Podophyllotoxin is used to produce two other drugs with different mechanisms of action: etoposide and teniposide . Topoisomerase inhibitors are drugs that affect the activity of two enzymes: topoisomerase I and topoisomerase II . When the DNA double-strand helix is unwound, during DNA replication or transcription , for example,

2850-426: Is that they interrupt cell division . The most important subgroup is the anthracyclines and the bleomycins ; other prominent examples include mitomycin C and actinomycin . Among the anthracyclines, doxorubicin and daunorubicin were the first, and were obtained from the bacterium Streptomyces peucetius . Derivatives of these compounds include epirubicin and idarubicin . Other clinically used drugs in

2945-455: Is the primary cause for their anti-cancer effects. DNA is made of two strands and the molecules may either bind twice to one strand of DNA (intrastrand crosslink) or may bind once to both strands (interstrand crosslink). If the cell tries to replicate crosslinked DNA during cell division , or tries to repair it, the DNA strands can break. This leads to a form of programmed cell death called apoptosis . Alkylating agents will work at any point in

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3040-601: The Buffalo Niagara Medical Campus "BNMC," and created the University at Buffalo Department of Structural Biology. Dr. George DeTitta was appointed Executive Director and CEO and Dr. Walter Pangborn was appointed to Executive Vice President. Shortly thereafter, four new scientists were added. As the University at Buffalo and Roswell Park Comprehensive Cancer Center , both members of BNMC, began plans to construct new facilities, HWI joined to form

3135-562: The CEO position on February 1, 2001, and then as chairman at the annual meeting on May 17 during which he was replaced by Henry Meyer. In October 2008, Key received approximately $ 2.5 billion (~$ 3.47 billion in 2023) in investment from the Troubled Asset Relief Program . In March 2011, Key was one of the last major banks to pay back TARP funds. In May 2011, Key made history by naming Beth E. Mooney, previously

3230-832: The PICC line . These have a lower infection risk, are much less prone to phlebitis or extravasation , and eliminate the need for repeated insertion of peripheral cannulae. Isolated limb perfusion (often used in melanoma ), or isolated infusion of chemotherapy into the liver or the lung have been used to treat some tumors. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumor sites without causing overwhelming systemic damage. These approaches can help control solitary or limited metastases, but they are by definition not systemic, and, therefore, do not treat distributed metastases or micrometastases . Topical chemotherapies, such as 5-fluorouracil , are used to treat some cases of non-melanoma skin cancer . If

3325-399: The amino , carboxyl , sulfhydryl , and phosphate groups in biologically important molecules. Non-classical alkylating agents include procarbazine and hexamethylmelamine. Anti-metabolites are a group of molecules that impede DNA and RNA synthesis. Many of them have a similar structure to the building blocks of DNA and RNA. The building blocks are nucleotides ; a molecule comprising

3420-521: The immune system , often by paralysing the bone marrow and leading to a decrease of white blood cells , red blood cells , and platelets . Anemia and thrombocytopenia may require blood transfusion . Neutropenia (a decrease of the neutrophil granulocyte count below 0.5 x 10 / litre ) can be improved with synthetic G-CSF ( granulocyte -colony-stimulating factor, e.g., filgrastim , lenograstim , efbemalenograstim alfa ). In very severe myelosuppression , which occurs in some regimens, almost all

3515-491: The regional economy of Cleveland , having 6,400 employees. In 2019, KeyBank announced it will be opening its first tellerless branch on May 13, 2019, in Boulder, Colorado . Instead of teller lines, the branch features private offices where clients can interact with bankers trained as "financial wellness consultants". In September 2019, Christopher Gorman was appointed president. On May 1, 2020, Christopher M. Gorman assumed

3610-468: The 5-FU clinical study cited above, people whose dose was adjusted to achieve a pre-determined target exposure realized an 84% improvement in treatment response rate and a six-month improvement in overall survival (OS) compared with those dosed by BSA. In the same study, investigators compared the incidence of common 5-FU-associated grade 3/4 toxicities between the dose-adjusted people and people dosed per BSA. The incidence of debilitating grades of diarrhea

3705-597: The BSA-dosed group to 70% in the dose-adjusted group. Median progression free survival (PFS) and overall survival (OS) both improved by six months in the dose adjusted group. One approach that can help clinicians individualize chemotherapy dosing is to measure the drug levels in blood plasma over time and adjust dose according to a formula or algorithm to achieve optimal exposure. With an established target exposure for optimized treatment effectiveness with minimized toxicities, dosing can be personalized to achieve target exposure and optimal results for each person. Such an algorithm

3800-879: The Buffalo Life Sciences Complex which is located in the heart of the BNMC adjacent to the UB and Roswell Park sites. CannonDesign was retained along with architect Mehrdad Yazdani to design a research and office complex and construction of the Structural Biology Research Center began in August 2003, through the support of New York State , the Federal Government, local foundations, community leaders, and individuals, as well as financing through KeyBank . BWI moved into

3895-746: The Midwest and Northeast United States, though also operates in the Pacific Northwest as well as in Alaska, Colorado, Texas and Utah. KeyBank is the primary subsidiary of KeyCorp, which was formed in 1994 through the merger of Society Corporation of Cleveland, Ohio ("Society Bank") and KeyCorp ("Old KeyCorp") of Albany, New York . The merger briefly made Key the 10th largest US bank. Its roots trace back to Commercial Bank of Albany, New York in 1825 and Cleveland's Society for Savings, founded in 1849. Society For Savings originated in 1849 as

Hauptman-Woodward Medical Research Institute - Misplaced Pages Continue

3990-613: The Nobel prize in chemistry in 1985. In 1999, the Institute received a three-year $ 1.5 million (equivalent to $ 2,744,000 in 2023) challenge grant from the John R. Oishei Foundation along with a $ 750,000 (equivalent to $ 1,372,000 in 2023) award from the Margaret L. Wendt Foundation that established a Structural Biology Center at HWI. All aspects of structural research from isolating

4085-410: The activity of topoisomerase II, and therefore prevent DNA synthesis and translation because the DNA cannot unwind properly. This group includes novobiocin , merbarone, and aclarubicin , which also have other significant mechanisms of action. The cytotoxic antibiotics are a varied group of drugs that have various mechanisms of action. The common theme that they share in their chemotherapy indication

4180-560: The adjacent unopened DNA winds tighter (supercoils), like opening the middle of a twisted rope. The stress caused by this effect is in part aided by the topoisomerase enzymes. They produce single- or double-strand breaks into DNA, reducing the tension in the DNA strand. This allows the normal unwinding of DNA to occur during replication or transcription. Inhibition of topoisomerase I or II interferes with both of these processes. Two topoisomerase I inhibitors, irinotecan and topotecan , are semi-synthetically derived from camptothecin , which

4275-405: The anthracycline group are pirarubicin , aclarubicin , and mitoxantrone . The mechanisms of anthracyclines include DNA intercalation (molecules insert between the two strands of DNA), generation of highly reactive free radicals that damage intercellular molecules and topoisomerase inhibition. Actinomycin is a complex molecule that intercalates DNA and prevents RNA synthesis . Bleomycin,

4370-638: The assembly of tubulin into microtubules. The original vinca alkaloids are natural products that include vincristine and vinblastine . Following the success of these drugs, semi-synthetic vinca alkaloids were produced: vinorelbine (used in the treatment of non-small-cell lung cancer ), vindesine , and vinflunine . These drugs are cell cycle -specific. They bind to the tubulin molecules in S-phase and prevent proper microtubule formation required for M-phase . Taxanes are natural and semi-synthetic drugs. The first drug of their class, paclitaxel ,

4465-523: The bank in 1997–1999 (i.e. Wyoming , Florida , and Long Island ), and credit card operations to The Associates in 2000 (which was quickly thereafter acquired by Citigroup ). But Gillespie was attempting to increase fee-income by acquiring high-growth businesses, including McDonald and equipment financing firm Leastec, and decreasing the exposure to the bank's shrinking population base in its primary footprint, so-called rust belt states such as Ohio , Michigan , and Indiana . Gillespie resigned from

4560-510: The bank sidestep many depressions and financial panics. In 1958, Society converted from a mutual to a public company , which enabled it to grow quickly by acquiring 12 community banks between 1958 and 1978 under the banner Society National Bank . It went through another growth spurt from 1979 to 1989, as it acquired dozens of small banks and completed four mergers worth one billion dollars, most notably Cleveland-based Central National Bank in 1986. In 1987, Society CEO Gordon E. Heffern retired and

4655-859: The bank's president, as the first female Chairman and CEO of a top 20 bank. In January 2012, Key acquired 37 former HSBC Bank USA branches in Upstate New York from First Niagara Bank for $ 110 million. In May 2013, the company acquired mortgage servicing rights from Bank of America . In January 2015, KeyBank participated in the construction debt financing syndicate behind the Balko Wind Project purchased from Apex Clean Energy by D.E. Shaw Renewable Investments. On July 29, 2016, KeyCorp acquired First Niagara Bank for $ 4.1 billion (~$ 5.1 billion in 2023) in cash and stock. The deal strengthened Key's position in Upstate New York and New England , as well as entering Pennsylvania for

4750-645: The bone marrow stem cells (cells that produce white and red blood cells ) are destroyed, meaning allogenic or autologous bone marrow cell transplants are necessary. (In autologous BMTs, cells are removed from the person before the treatment, multiplied and then re-injected afterward; in allogenic BMTs, the source is a donor.) However, some people still develop diseases because of this interference with bone marrow. Although people receiving chemotherapy are encouraged to wash their hands, avoid sick people, and take other infection-reducing steps, about 85% of infections are due to naturally occurring microorganisms in

4845-475: The cancer cells. Following this, cell cycle arrest occurs, which induces programmed cell death ( apoptosis ). These drugs can also affect blood vessel growth , an essential process that tumours utilise in order to grow and metastasise. Vinca alkaloids are derived from the Madagascar periwinkle , Catharanthus roseus , formerly known as Vinca rosea . They bind to specific sites on tubulin, inhibiting

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4940-589: The cancer has central nervous system involvement, or with meningeal disease, intrathecal chemotherapy may be administered. Chemotherapeutic techniques have a range of side effects that depend on the type of medications used. The most common medications affect mainly the fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines. Chemotherapy-related toxicities can occur acutely after administration, within hours or days, or chronically, from weeks to years. Virtually all chemotherapeutic regimens can cause depression of

5035-933: The cell cycle and thus are known as cell cycle-independent drugs. For this reason, the effect on the cell is dose dependent; the fraction of cells that die is directly proportional to the dose of drug. The subtypes of alkylating agents are the nitrogen mustards , nitrosoureas , tetrazines , aziridines , cisplatins and derivatives, and non-classical alkylating agents. Nitrogen mustards include mechlorethamine , cyclophosphamide , melphalan , chlorambucil , ifosfamide and busulfan . Nitrosoureas include N-Nitroso-N-methylurea (MNU), carmustine (BCNU), lomustine (CCNU) and semustine (MeCCNU), fotemustine and streptozotocin . Tetrazines include dacarbazine , mitozolomide and temozolomide . Aziridines include thiotepa , mytomycin and diaziquone (AZQ). Cisplatin and derivatives include cisplatin , carboplatin and oxaliplatin . They impair cell function by forming covalent bonds with

5130-415: The city of Albany and then-Governor Mario Cuomo openly fretted that the merger would be bad for the state capital since Key and its subsidiaries owned or leased more than 10% of Albany's commercial office space. By 2014, only about 225 non-branch employees were still based in Albany at the former KeyCorp Tower. Society and Key completed the merger on March 1, 1994, after regulatory approval. Although it

5225-413: The computer systems and technology expertise to combine the two banks, along with Chief Information Officer Allen J. Gula. Riley also lamented the modest Albany International Airport , which lost service from several major airlines in the 1980's and complicated air travel for Key executives. Ohio also had lower state taxes than New York. Lastly, Society had recently built Society Center (now Key Tower ),

5320-629: The core of what had been Marine Midland Bank , old KeyCorp's longtime rival. Five years earlier, First Niagara had acquired most of the upstate New York branch network of HSBC Bank USA , which had changed its name from Marine Midland in 1999; as mentioned above, Key had acquired 37 HSBC branches in 2012. As part of the transaction, 18 First Niagara branches in Erie and Niagara Counties in New York were sold to Northwest Savings Bank for antitrust reasons. KeyBank continues to play an important role in

5415-452: The dose is too low, it will be ineffective against the tumor, whereas, at excessive doses, the toxicity ( side-effects ) will be intolerable to the person receiving it. The standard method of determining chemotherapy dosage is based on calculated body surface area (BSA). The BSA is usually calculated with a mathematical formula or a nomogram , using the recipient's weight and height, rather than by direct measurement of body area. This formula

5510-613: The end of 1995. He decided to accelerate it by four months, however, instead stepping down on September 1, 1995. Gillespie took the helm as CEO and later chairman, allowing his protege Henry Meyer to become COO and later president. While still integrating Society Bank and KeyBank, Gillespie attempted to turn Key into a financial services powerhouse. Between 1995 and 2001, Gillespie initiated nine significant acquisitions and 6 divestitures. In late 1998, Key bought Cleveland-based brokerage firm, McDonald & Co. for $ 653 million (~$ 1.14 billion in 2023) in stock. The McDonald acquisition

5605-622: The enzyme is inhibited by methotrexate, the cellular levels of folate coenzymes diminish. These are required for thymidylate and purine production, which are both essential for DNA synthesis and cell division. Pemetrexed is another anti-metabolite that affects purine and pyrimidine production, and therefore also inhibits DNA synthesis. It primarily inhibits the enzyme thymidylate synthase , but also has effects on DHFR, aminoimidazole carboxamide ribonucleotide formyltransferase and glycinamide ribonucleotide formyltransferase . The fluoropyrimidines include fluorouracil and capecitabine . Fluorouracil

5700-443: The enzymes involved in DNA synthesis, they prevent mitosis because the DNA cannot duplicate itself. Also, after misincorporation of the molecules into DNA, DNA damage can occur and programmed cell death ( apoptosis ) is induced. Unlike alkylating agents, anti-metabolites are cell cycle dependent. This means that they only work during a specific part of the cell cycle, in this case S-phase (the DNA synthesis phase). For this reason, at

5795-529: The first time with a presence in both Philadelphia and Pittsburgh . The deal made Key one of the largest banks in Pittsburgh, and gave it branches that were once part of the crosstown rival National City Corp. , which Key tried to acquire from PNC Financial Services following the National City acquisition by PNC in 2008 before being outbid by First Niagara. As a result, KeyCorp now held much of

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5890-582: The formula only takes into account the individual's weight and height. Drug absorption and clearance are influenced by multiple factors, including age, sex, metabolism, disease state, organ function, drug-to-drug interactions, genetics, and obesity, which have major impacts on the actual concentration of the drug in the person's bloodstream. As a result, there is high variability in the systemic chemotherapy drug concentration in people dosed by BSA, and this variability has been demonstrated to be more than ten-fold for many drugs. In other words, if two people receive

5985-417: The gene that codes for a protein of interest to applying the latest crystallographic methods are now possible here. Through this Center, HWI scientists were able to create new and improved crystal growth methods including the development of a novel and patented high-throughput robotic crystallization technique for expediting and optimizing the crystallization process. In 2001, BWI became a founding partner of

6080-536: The immune system is suppressed to a critically low level. In Japan , the government has approved the use of some medicinal mushrooms like Trametes versicolor , to counteract depression of the immune system in people undergoing chemotherapy. Trilaciclib is an inhibitor of cyclin-dependent kinase 4/6 approved for the prevention of myelosuppression caused by chemotherapy. The drug is given before chemotherapy to protect bone marrow function. Due to immune system suppression, neutropenic enterocolitis (typhlitis)

6175-417: The lining of the digestive tract), and alopecia (hair loss). Because of the effect on immune cells (especially lymphocytes), chemotherapy drugs often find use in a host of diseases that result from harmful overactivity of the immune system against self (so-called autoimmunity ). These include rheumatoid arthritis , systemic lupus erythematosus , multiple sclerosis , vasculitis and many others. There are

6270-497: The new facility in April 2005, and have since recruited four additional scientists to the facility. On April 1, 2008, George DeTitta stepped down as CEO to return to full-time work in the lab and on July 1, 2008, Eaton E. (Ed) Lattman, formerly a Professor of Biophysics at Johns Hopkins University became HWI's new CEO. Ed was previously the dean of research and graduate education at Hopkins. On December 1, 2014, Dr. Edward H. Snell

6365-712: The non-specific use of intracellular poisons to inhibit mitosis (cell division) or to induce DNA damage (so that DNA repair can augment chemotherapy). This meaning excludes the more-selective agents that block extracellular signals ( signal transduction ). Therapies with specific molecular or genetic targets, which inhibit growth-promoting signals from classic endocrine hormones (primarily estrogens for breast cancer and androgens for prostate cancer), are now called hormonal therapies . Other inhibitions of growth-signals, such as those associated with receptor tyrosine kinases , are targeted therapy . The use of drugs (whether chemotherapy, hormonal therapy, or targeted therapy)

6460-412: The person vomits frequently, because of gastrointestinal damage. This can result in rapid weight loss, or occasionally in weight gain, if the person eats too much in an effort to allay nausea or heartburn. Weight gain can also be caused by some steroid medications. These side-effects can frequently be reduced or eliminated with antiemetic drugs. Low-certainty evidence also suggests that probiotics may have

6555-825: The person's own gastrointestinal tract (including oral cavity ) and skin. This may manifest as systemic infections, such as sepsis , or as localized outbreaks, such as Herpes simplex , shingles , or other members of the Herpesviridea . The risk of illness and death can be reduced by taking common antibiotics such as quinolones or trimethoprim/sulfamethoxazole before any fever or sign of infection appears. Quinolones show effective prophylaxis mainly with hematological cancer. However, in general, for every five people who are immunosuppressed following chemotherapy who take an antibiotic, one fever can be prevented; for every 34 who take an antibiotic, one death can be prevented. Sometimes, chemotherapy treatments are postponed because

6650-522: The person, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, intravenous chemotherapy may be given on either an inpatient or an outpatient basis. For continuous, frequent or prolonged intravenous chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access. Commonly used systems are the Hickman line , the Port-a-Cath , and

6745-585: The region's capital. That, coupled with increasing competition for acquisition targets, caused Riley to essentially abandon the Northeast. Instead, he began searching for prey in the Pacific Northwest. Riley found a target-rich environment in rural and underserved areas. He snapped up small banks in Wyoming , Idaho , Utah , Washington and Oregon . He even went so far as to buy two banks in Alaska , for which he

6840-503: The right dose to achieve optimal treatment effectiveness with minimized toxic side effects. Some people are overdosed while others are underdosed. For example, in a randomized clinical trial, investigators found 85% of metastatic colorectal cancer patients treated with 5-fluorouracil (5-FU) did not receive the optimal therapeutic dose when dosed by the BSA standard—68% were underdosed and 17% were overdosed. There has been controversy over

6935-547: The role of Chairman, Chief Executive Officer, and President of KeyCorp bringing more than 30 years of financial services experience to his role. In 2021, KeyBank originated 52,366 mortgages worth $ 25 billion (~$ 27.7 billion in 2023). KeyBank provided $ 21 Million in financing options for seniors in a senior housing initiative based in New York in June of 2023. However, in May earlier that year, multiple groups claim that they broke

7030-429: The same dose of a given drug based on BSA, the concentration of that drug in the bloodstream of one person may be 10 times higher or lower compared to that of the other person. This variability is typical with many chemotherapy drugs dosed by BSA, and, as shown below, was demonstrated in a study of 14 common chemotherapy drugs. The result of this pharmacokinetic variability among people is that many people do not receive

7125-478: The so-called rust belt states of Ohio , Michigan , and Indiana . The merger was announced in early October 1993. This time it was Riley who made the first move; he called Gillespie while recuperating at his Albany home after breaking his hip in a horse-riding accident in Wyoming. The two quickly sketched out the deal. The banks were roughly the same size in assets and had very little geographic overlap, so it

7220-461: The starting points for the design of better drugs. HWI is also focused to developing highly trained researchers and in its role as the Department of Structural and Computational Biology for the University at Buffalo , the Institute typically trains about a dozen PhD students and sponsors internship programs for high school and college students. The Hauptman-Woodward Medical Research Institute

7315-473: The use of BSA to calculate chemotherapy doses for people who are obese . Because of their higher BSA, clinicians often arbitrarily reduce the dose prescribed by the BSA formula for fear of overdosing . In many cases, this can result in sub-optimal treatment. Several clinical studies have demonstrated that when chemotherapy dosing is individualized to achieve optimal systemic drug exposure, treatment outcomes are improved and toxic side effects are reduced. In

7410-625: Was appointed CEO following eight years of service to HWI as a senior research scientist. In 2024 he transitioned to Chief Scientific Officer. Before joining HWI, Dr. Snell was a staff scientist in NASA ’s Structural Biology Laboratory at the Marshall Space Flight Center in Huntsville, Alabama . The institute has sponsored the award "Pioneer of Science". It also runs a popular annual wine tasting event where Riedel glassware

7505-743: Was flogged in the media and in banking circles. Unorthodox strategy aside, Riley quintupled Key's assets from $ 3 billion to $ 15 billion in just four years between 1985 and 1990. While the early 1990s recession rocked many banks, Key had ample capital. It bought the assets of two failed thrifts from the government: Empire Federal Savings and Loan and Goldome Savings Bank. In March 1992, it acquired Tacoma-based Puget Sound Bancorp for $ 807.2 million (~$ 1.57 billion in 2023) to bolster its presence in Washington. Also in 1992, Key acquired Home Federal Savings of Fort Collins, its first move into Colorado . Key soon amassed nearly 700 banking offices. The result

7600-478: Was founded in 1956 as the "Medical Foundation of Buffalo" and came into existence through the combined efforts of Dr. George F. Koepf, who provided the vision, and Helen Woodward Rivas, who provided generous financial support. Koepf was a physician and endocrinologist whose interest in research began during his second year at medical school and continued at Johns Hopkins University . After leaving Johns Hopkins, he returned to practice medicine in Buffalo and became

7695-428: Was frustrated with the pace of achieving his goal of running a large bank. The head of KeyBank of Washington, Hans Harjo, was pushed out over an apparent dispute to move its headquarters from Seattle to Tacoma . It also became clear that Key had to undertake a technology infrastructure upgrade to connect its far-flung offices. Meanwhile, Society was in search of higher growth and longed to expand its presence outside of

7790-399: Was making all the moves to cover up poor performance, although in hindsight that appears to be far from the truth. The concept was dubbed "burning the furniture", implying that Key would sell an asset to obfuscate earnings. For instance, Key sold its residential mortgage servicing to Countrywide Financial (now Bank of America Home Loans ) in 1995, shareholder services in 1996, various chunks of

7885-438: Was originally derived in a 1916 study and attempted to translate medicinal doses established with laboratory animals to equivalent doses for humans. The study only included nine human subjects. When chemotherapy was introduced in the 1950s, the BSA formula was adopted as the official standard for chemotherapy dosing for lack of a better option. The validity of this method in calculating uniform doses has been questioned because

7980-570: Was originally extracted from Taxus brevifolia , the Pacific yew. Now this drug and another in this class, docetaxel , are produced semi-synthetically from a chemical found in the bark of another yew tree, Taxus baccata . Podophyllotoxin is an antineoplastic lignan obtained primarily from the American mayapple ( Podophyllum peltatum ) and Himalayan mayapple ( Sinopodophyllum hexandrum ). It has anti-microtubule activity, and its mechanism

8075-412: Was reduced from 18% in the BSA-dosed group to 4% in the dose-adjusted group and serious hematologic side effects were eliminated. Because of the reduced toxicity, dose-adjusted patients were able to be treated for longer periods of time. BSA-dosed people were treated for a total of 680 months while people in the dose-adjusted group were treated for a total of 791 months. Completing the course of treatment

8170-598: Was reported that a researcher at the Hauptman-Woodward Medical Research Institute had moved a step closer to a cure, and possibly the prevention, of the most common type of breast cancer. In 1994, the Medical Foundation was renamed the Hauptman-Woodward Medical Research Institute. The name "Hauptman" comes from Herbert A. Hauptman , who pioneered mathematical techniques for determining atomic structure from X-ray diffraction. For this discovery, Hauptman and Jerome Karle were awarded

8265-488: Was succeeded by Robert W. Gillespie, who, although just 42, was a major figure and part of the office of the chairman for more than 5 years. Gillespie was also named chairman. Gillespie started as a teller with Society to earn money while he was finishing his graduate studies. Society Corporation acquired Toledo, Ohio -based Trustcorp in 1990 and holding company AmeriTrust Corporation , in September 1991. Ameritrust

8360-437: Was the 29th largest U.S. bank with $ 26 billion in assets, while Society was the 25th largest with $ 32 billion in assets. Both needed a merger to improve their prospects. For its part, Key needed a succession plan due to the lack of an obvious successor to the 62-year-old Riley. In one week in June 1993, the bench had become barren – Chief Banking Officer James Waterston, hired the year before, quit and publicly stated that he

8455-496: Was the largest non-banking deal in both size and impact on Key. McDonald was sold to the U.S. investment arm of UBS AG in 2007 for roughly $ 280 million (~$ 396 million in 2023). As a result, Key began processing all subsequent securities transactions under its new broker-dealer name, "KeyBanc Capital Markets Inc", in April 2007. However, investors became wary of all the Gillespie-era deals. Some believed that Gillespie

8550-566: Was the nominal survivor; the merged bank was headquartered in Cleveland and retains Society's pre-1994 stock price history. The Society name continued to be used in Society's former footprint for an additional two more years before it was retired in June 1996 and the charters were merged. Riley became chairman and CEO of the "new" KeyCorp, with Gillespie as president and chief operating officer . Despite assurances from both Riley and Gillespie,

8645-507: Was the successor to Cleveland Trust Company , which was Ohio's largest bank during the 1940s through the late 1970s. The AmeriTrust deal established Society as a large regional bank. However, its footing became unsteady due to bad real estate loans , forcing the resignation of AmeriTrust chairman Jerry V. Jarrett in 1990. Moreover, Gillespie was able to outbid Society's larger rival, National City Corp. , which also bid for Cleveland Trust. In 1825, New York Governor DeWitt Clinton signed

8740-586: Was touted as a merger of equals, Key and Society were an odd couple. As mentioned above, Key was a decentralized community bank combining two banking networks—an eastern network in New England and upstate New York and a western one in the Rockies and Pacific Northwest—within a single corporate structure. Society, in contrast, was a classic big-city commercial bank with a centralized structure largely concentrated in three states. Riley planned to retire as CEO at

8835-414: Was touted as an out-of-market merger in which few branches needed to be sold off. It created a $ 58 billion banking behemoth with a footprint that literally stretched from Portland, Maine to Portland, Oregon . Furthermore, the deal plugged many of the perceived holes for both partners. The soft-spoken Gillespie was just 49 and Society had cultivated a deep bench of lieutenants. More importantly, Society had

8930-457: Was two separate banking networks united under a single corporate umbrella. However, this strategy actually worked well for Key. Not only was it insulated from regional economic downturns, but it avoided bad loans by lending primarily to customers in the areas it served. When Key acquired a bank, it retained most of the bank's personnel. Riley argued that a bank that entered new territory and "start(ed) shuffling people around" could not brand itself as

9025-508: Was used in the clinical trials cited above and resulted in significantly improved treatment outcomes. Oncologists are already individualizing dosing of some cancer drugs based on exposure. Carboplatin and busulfan dosing rely upon results from blood tests to calculate the optimal dose for each person. Simple blood tests are also available for dose optimization of methotrexate , 5-FU, paclitaxel , and docetaxel . The serum albumin level immediately prior to chemotherapy administration

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